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Patranabis S. Recent Advances in the miRNA-Mediated Regulation of Neuronal Differentiation and Death. Neuromolecular Med 2024; 26:52. [PMID: 39648193 DOI: 10.1007/s12017-024-08820-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 11/25/2024] [Indexed: 12/10/2024]
Abstract
The review aims to focus on the role of miRNA in gene regulation, related to differentiation and apoptosis of neurons, focusing on the array of miRNAs involved in the processes. miRNAs are a known class of small regulatory RNAs, which in association with RNA processing bodies, play major roles in different cellular events, such as neurogenesis and neuronal differentiation. miRNAs function in controlling neuronal events by targeting different important molecules of cellular signalling. The post-translational modification of Ago2 is crucial in modulating the neurons' miRNA-mediated regulation. Thus, understanding the crosstalk between cellular signalling and miRNA activity affecting neuronal events is very important to decipher novel targets and related signalling pathways, involved in neuronal survival and neurodegeneration.
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Cotino‐Nájera S, García‐Villa E, Cruz‐Rosales S, Gariglio P, Díaz‐Chávez J. The role of Lin28A and Lin28B in cancer beyond Let-7. FEBS Lett 2024; 598:2963-2979. [PMID: 39152528 PMCID: PMC11665955 DOI: 10.1002/1873-3468.15004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 07/02/2024] [Accepted: 07/21/2024] [Indexed: 08/19/2024]
Abstract
Lin28A and Lin28B are paralogous RNA-binding proteins that play fundamental roles in development and cancer by regulating the microRNA family of tumor suppressor Let-7. Although Lin28A and Lin28B share some functional similarities with Let-7 inhibitors, they also have distinct expression patterns and biological functions. Increasing evidence indicates that Lin28A and Lin28B differentially impact cancer stem cell properties, epithelial-mesenchymal transition, metabolic reprogramming, and other hallmarks of cancer. Therefore, it is important to understand the overexpression of Lin28A and Lin28B paralogs in specific cancer contexts. In this review, we summarize the main similarities and differences between Lin28A and Lin28B, their implications in different cellular processes, and their role in different types of cancer. In addition, we provide evidence of other specific targets of each lin28 paralog, as well as the lncRNAs and miRNAs that promote or inhibit its expression, and how this impacts cancer development and progression.
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Affiliation(s)
- Sandra Cotino‐Nájera
- Departamento de Genética y Biología MolecularCentro de Investigación y de Estudios Avanzados (CINVESTAV)Mexico CityMexico
| | - Enrique García‐Villa
- Departamento de Genética y Biología MolecularCentro de Investigación y de Estudios Avanzados (CINVESTAV)Mexico CityMexico
| | - Samantha Cruz‐Rosales
- Departamento de Genética y Biología MolecularCentro de Investigación y de Estudios Avanzados (CINVESTAV)Mexico CityMexico
| | - Patricio Gariglio
- Departamento de Genética y Biología MolecularCentro de Investigación y de Estudios Avanzados (CINVESTAV)Mexico CityMexico
| | - José Díaz‐Chávez
- Departamento de Biología Celular, Facultad de CienciasUNAMMexico CityMexico
- Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones BiomédicasUNAM/Instituto Nacional de CancerologíaMexico CityMexico
- Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la SaludMexico
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3
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Kordacka J, Gruszka R, Zakrzewska M. Serum microRNA qPCR profiling and validation indicate upregulation of circulating miR-145-5p and miR-26a-5p in migraineurs. J Headache Pain 2024; 25:198. [PMID: 39551757 PMCID: PMC11571994 DOI: 10.1186/s10194-024-01908-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 11/07/2024] [Indexed: 11/19/2024] Open
Abstract
BACKGROUND In recent years, miRNAs found in biological fluids have gained interest as biomarkers of numerous conditions, including migraine. This study aimed to identify differences in the levels of circulating miRNAs in the serum of migraineurs as compared to healthy controls, as well as between patients with different types of migraine and during the ictal and nonictal phases of the condition. METHODS The screening phase of the study included serum from 13 migraine patients and 13 sex and age matched controls. A panel of 179 miRNAs was analysed using locked nucleic acid SYBR based qPCR. Based on statistical analysis (U Mann-Whitney test) and data from existing literature, nine miRNAs were selected for validation by TaqMan qPCR in an independent cohort of 26 migraineurs and eleven healthy controls. For comparison between the study and control group, U Mann-Whitney test was performed. The differences between patients with chronic and episodic migraine, migraine with and without aura and in ictal and nonictal phases were analysed with Kruskal-Wallis test. The results were corrected for multiple comparisons using Benjamini-Hochberg method. In all analysis p value ≤ 0,05 was considered as significant. RESULTS Two miRNAs, miR-145-5p and miR-26a-5p were significantly upregulated in serum of migraineurs compared to healthy controls. MiRNA-19a-3p was downregulated in patients currently experiencing migraine headache compared to those in the interictal period. No differences were found between patients with different migraine types. CONCLUSION The results of our study add to the growing body of evidence for dysregulation of the circulating miRNA profile by migraine. They are further supported by previous reports on differential expression of miR-145-5p, miR-26a-5p and miR-19a-3p in migraineurs. However, more research on larger populations is needed to validate these findings, as well as elucidate the role of circulating miRNAs in the condition. Moreover, to wholly explore the biomarker potential of miRNAs, migraine patients should not only be compared to healthy controls but also to populations with different headache disorders.
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Affiliation(s)
- Joanna Kordacka
- Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
| | - Renata Gruszka
- Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Magdalena Zakrzewska
- Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland
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Sane S, Ebrahimi V, Shirvani Farsani Z, Ghafouri-Fard S. Assessment of Expression of lncRNAs in Autistic Patients. J Mol Neurosci 2024; 74:81. [PMID: 39186094 DOI: 10.1007/s12031-024-02258-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 08/17/2024] [Indexed: 08/27/2024]
Abstract
Autism is a severe neurodevelopmental condition with unknown pathobiology. Nevertheless, multiple pieces of evidence suggest long non-coding RNA (lncRNA) dysregulation may be a contributing factor to this disorder. We investigated the association between the expression of five specific lncRNAs and autism. Peripheral blood was collected from 30 children with autism and 41 healthy children. The expression levels of PCAT-29, lincRNA-ROR, LINC-PINT, lincRNA-p21, and PCAT-1 were calculated. Then, their significance as biomarkers was also evaluated. The expression of LincRNA-ROR (27 times), LINC-PINT (5.26 times), LincRNA-p21 (4.54 times), PCAT-29 (16.66 times), and PCAT-1 (25 times) genes was significantly decreased in patients compared to the control group (p values < 0.05). According to the ROC curve analysis for each lncRNA, LincRNA-ROR, LINC-PINT, LincRNA-p21, PCAT-29, and PCAT-1 lncRNAs with diagnostic power of 0.85, 0.67, 0.64, 0.74, and 0.84, respectively, could be used as diagnostic biomarkers for autism. Additionally, significant positive correlations were reported between expression levels of PCAT-1 and PCAT-29 genes. Moreover, a positive correlation was detected between expression levels of lincRNA-ROR and patients' age. The current study shows further pieces of evidence for deregulation of lncRNAs in autistic patients that show these lncRNAs may play an important part in the pathogenesis of ASD. However, the role of lncRNA in the neurobiology of autism needs to be investigated further.
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Affiliation(s)
- Saba Sane
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Vera Ebrahimi
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Zeinab Shirvani Farsani
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Aria H, Azizi M, Nazem S, Mansoori B, Darbeheshti F, Niazmand A, Daraei A, Mansoori Y. Competing endogenous RNAs regulatory crosstalk networks: The messages from the RNA world to signaling pathways directing cancer stem cell development. Heliyon 2024; 10:e35208. [PMID: 39170516 PMCID: PMC11337742 DOI: 10.1016/j.heliyon.2024.e35208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 07/08/2024] [Accepted: 07/24/2024] [Indexed: 08/23/2024] Open
Abstract
Cancer stem cells (CSCs) are one of the cell types that account for cancer heterogeneity. The cancer cells arrest in G0 and generate non-CSC progeny through self-renewal and pluripotency, resulting in tumor recurrence, metastasis, and resistance to chemotherapy. They can stimulate tumor relapse and re-grow a metastatic tumor. So, CSCs is a promising target for eradicating tumors, and developing an anti-CSCs therapy has been considered. In recent years competing endogenous RNA (ceRNA) has emerged as a significant class of post-transcriptional regulators that affect gene expression via competition for microRNA (miRNA) binding. Furthermore, aberrant ceRNA expression is associated with tumor progression. Recent findings show that ceRNA network can cause tumor progression through the effect on CSCs. To overcome therapeutic resistance due to CSCs, we need to improve our current understanding of the mechanisms by which ceRNAs are implicated in CSC-related relapse. Thus, this review was designed to discuss the role of ceRNAs in CSCs' function. Targeting ceRNAs may open the path for new cancer therapeutic targets and can be used in clinical research.
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Affiliation(s)
- Hamid Aria
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahdieh Azizi
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shima Nazem
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Behnam Mansoori
- Pediatrics Department, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Farzaneh Darbeheshti
- Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Anoosha Niazmand
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abdolreza Daraei
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Yaser Mansoori
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
- Department of Medical Genetics, Fasa University of Medical Sciences, Fasa, Iran
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Luo L, Xu N, Fan W, Wu Y, Chen P, Li Z, He Z, Liu H, Lin Y, Zheng G. The TGFβ2-Snail1-miRNA TGFβ2 Circuitry is Critical for the Development of Aggressive Functions in Breast Cancer. Clin Transl Med 2024; 14:e1558. [PMID: 38299307 PMCID: PMC10831563 DOI: 10.1002/ctm2.1558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 01/04/2024] [Accepted: 01/09/2024] [Indexed: 02/02/2024] Open
Abstract
There have been contradictory reports on the biological role of transforming growth factor-βs (TGFβs) in breast cancer (BC), especially with regard to their ability to promote epithelial-mesenchymal transition (EMT). Here, we show that TGFβ2 is preferentially expressed in mesenchymal-like BCs and maintains the EMT phenotype, correlating with cancer stem cell-like characteristics, growth, metastasis and chemo-resistance and predicting worse clinical outcomes. However, this is only true in ERα- BC. In ERα+ luminal-type BC, estrogen receptor interacts with p-Smads to block TGFβ signalling. Furthermore, we also identify a microRNAs (miRNAs) signature (miRNAsTGFβ2 ) that is weakened in TGFβ2-overexpressing BC cells. We discover that TGFβ2-Snail1 recruits enhancer of zeste homolog-2 to convert miRNAsTGFβ2 promoters from an active to repressive chromatin configuration and then repress miRNAsTGFβ2 transcription, forming a negative feedback loop. On the other hand, miRNAsTGFβ2 overexpression reverses the mesenchymal-like traits in agreement with the inhibition of TGFβ2-Snail1 signalling in BC cells. These findings clarify the roles of TGFβ2 in BC and suggest novel therapeutic strategies based on the TGFβ2-Snail1-miRNAsTGFβ2 loop for a subset type of human BCs.
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Affiliation(s)
- Liyun Luo
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Ning Xu
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Weina Fan
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Yixuan Wu
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Pingping Chen
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Zhihui Li
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Zhimin He
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Hao Liu
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Ying Lin
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
| | - Guopei Zheng
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseGuangzhouChina
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Zvozilova A, Reichova A, Mach M, Bakos J, Koprdova R. Effect of a New Substance with Pyridoindole Structure on Adult Neurogenesis, Shape of Neurons, and Behavioral Outcomes in a Chronic Mild Stress Model in Rats. Int J Mol Sci 2024; 25:845. [PMID: 38255918 PMCID: PMC10815319 DOI: 10.3390/ijms25020845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/07/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Despite an accumulating number of studies, treatments for depression are currently insufficient. Therefore, the search for new substances with antidepressant potential is very important. In this study, we hypothesized that treatment with a newly synthesized pyridoindole derivative compound SMe1EC2M3 would result in protective and antidepressant-like effects on behavioral outcomes and reverse the impaired adult hippocampal neurogenesis caused by chronic mild stress (CMS). We found that chronic administration of 5 mg/kg and 25 mg/kg SMe1EC2M3 to adult Sprague Dawley rats ameliorated the consequences of CMS on immobility and swimming time in a forced swim test. A slight sedative effect of the highest dose of SMe1EC2M3 in the nonstress group was observed in the open field. SMe1EC2M3 in the highest dose ameliorated CMS-induced decreases in the sucrose preference test. Administration of SMe1EC2M3 significantly increased SOX2-positive cells in the hippocampal dentate gyrus (DG) in CMS compared to control animals. A significant reduction in glial fibrillary acid protein (GFAP)-positive cells in the DG of CMS compared to control animals was observed. Administration of both 5 and 25 mg/kg SMe1EC2M3 significantly increased signal of GFAP-positive cells in the DG of CMS animals. No such effects of SMe1EC2M3 were observed in the cornu ammonis hippocampal area. Additionally, we found that incubation of primary hippocampal neurons in the presence of 1.50 µM SMe1EC2M3 significantly stimulated the length of neurites. Overall, we found that the negative effects of CMS on depression-like behavior are partially reduced by the administration of SMe1EC2M3 and are associated with changes in hippocampal neurogenesis and neuronal differentiation. SMe1EC2M3 represents a potential drug candidate with positive neuroplastic effects and neurogenesis-associated effects in therapeutic approaches to depression.
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Affiliation(s)
- Alexandra Zvozilova
- Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia; (A.Z.); (R.K.)
| | - Alexandra Reichova
- Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia;
| | - Mojmir Mach
- Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia; (A.Z.); (R.K.)
| | - Jan Bakos
- Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia;
- Institute of Physiology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
| | - Romana Koprdova
- Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia; (A.Z.); (R.K.)
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Bassett C, Triplett H, Lott K, Howard KM, Kingsley K. Differential Expression of MicroRNA (MiR-27, MiR-145) among Dental Pulp Stem Cells (DPSCs) Following Neurogenic Differentiation Stimuli. Biomedicines 2023; 11:3003. [PMID: 38002003 PMCID: PMC10669296 DOI: 10.3390/biomedicines11113003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 11/03/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023] Open
Abstract
This study sought to evaluate the expression of previously identified microRNAs known to regulate neuronal differentiation in mesenchymal stem cells (MSCs), including miR-27, miR-125, miR-128, miR-135, miR-140, miR-145, miR-218 and miR-410, among dental pulp stem cells (DPSCs) under conditions demonstrated to induce neuronal differentiation. Using an approved protocol, n = 12 DPSCs were identified from an existing biorepository and treated with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), which were previously demonstrated to induce neural differentiation markers including Sox1, Pax6 and NFM among these DPSCs. This study revealed that some microRNAs involved in the neuronal differentiation of MSCs were also differentially expressed among the DPSCs, including miR-27 and miR-145. In addition, this study also revealed that administration of bFGF and EGF was sufficient to modulate miR-27 and miR-145 expression in all of the stimulus-responsive DPSCs but not among all of the non-responsive DPSCs-suggesting that further investigation of the downstream targets of these microRNAs may be needed to fully evaluate and understand these observations.
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Affiliation(s)
- Charlton Bassett
- School of Medicine, University of Nevada, Las Vegas 1700 West Charleston Boulevard, Las Vegas, NV 89106, USA; (C.B.); (H.T.); (K.L.)
| | - Hunter Triplett
- School of Medicine, University of Nevada, Las Vegas 1700 West Charleston Boulevard, Las Vegas, NV 89106, USA; (C.B.); (H.T.); (K.L.)
| | - Keegan Lott
- School of Medicine, University of Nevada, Las Vegas 1700 West Charleston Boulevard, Las Vegas, NV 89106, USA; (C.B.); (H.T.); (K.L.)
| | - Katherine M. Howard
- School of Dental Medicine, University of Nevada, Las Vegas 1001 Shadow Lane, Las Vegas, NV 89106, USA;
| | - Karl Kingsley
- School of Dental Medicine, University of Nevada, Las Vegas 1001 Shadow Lane, Las Vegas, NV 89106, USA;
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Lutfi Ismaeel G, Makki AlHassani OJ, S Alazragi R, Hussein Ahmed A, H Mohamed A, Yasir Jasim N, Hassan Shari F, Almashhadani HA. Genetically engineered neural stem cells (NSCs) therapy for neurological diseases; state-of-the-art. Biotechnol Prog 2023; 39:e3363. [PMID: 37221947 DOI: 10.1002/btpr.3363] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 04/28/2023] [Accepted: 05/01/2023] [Indexed: 05/25/2023]
Abstract
Neural stem cells (NSCs) are multipotent stem cells with remarkable self-renewal potential and also unique competencies to differentiate into neurons, astrocytes, and oligodendrocytes (ODCs) and improve the cellular microenvironment. In addition, NSCs secret diversity of mediators, including neurotrophic factors (e.g., BDNF, NGF, GDNF, CNTF, and NT-3), pro-angiogenic mediators (e.g., FGF-2 and VEGF), and anti-inflammatory biomolecules. Thereby, NSCs transplantation has become a reasonable and effective treatment for various neurodegenerative disorders by their capacity to induce neurogenesis and vasculogenesis and dampen neuroinflammation and oxidative stress. Nonetheless, various drawbacks such as lower migration and survival and less differential capacity to a particular cell lineage concerning the disease pathogenesis hinder their application. Thus, genetic engineering of NSCs before transplantation is recently regarded as an innovative strategy to bypass these hurdles. Indeed, genetically modified NSCs could bring about more favored therapeutic influences post-transplantation in vivo, making them an excellent option for neurological disease therapy. This review for the first time offers a comprehensive review of the therapeutic capability of genetically modified NSCs rather than naïve NSCs in neurological disease beyond brain tumors and sheds light on the recent progress and prospect in this context.
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Affiliation(s)
- Ghufran Lutfi Ismaeel
- Department of Pharmacology, College of Pharmacy, University of Al-Ameed, Karbala, Iraq
| | | | - Reem S Alazragi
- Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia
| | - Ammar Hussein Ahmed
- Department of Radiology and Sonar, College of Medical Techniques, Al-Farahidi University, Baghdad, Iraq
| | - Asma'a H Mohamed
- Intelligent Medical Systems Department, Al-Mustaqbal University College, Babylon, Iraq
| | - Nisreen Yasir Jasim
- Collage of Pharmacy, National University of Science and Technology, Dhi Qar, Iraq
| | - Falah Hassan Shari
- Department of Clinical Laboratory Sciences, College of Pharmacy, University of Basrah, Basrah, Iraq
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10
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Li W, Ji R, Lin Y, Cheng X, Tang Z, He H, Zhang L, Qin J, Tian M, Jin G, Zhang X. miR-6216 Regulates Neural Stem Cell Proliferation by Targeting RAB6B. Neurosci Res 2023:S0168-0102(23)00073-1. [PMID: 37059126 DOI: 10.1016/j.neures.2023.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/16/2023] [Accepted: 04/11/2023] [Indexed: 04/16/2023]
Abstract
Neural stem cells (NSCs) are a class of self-renewing, multipotent and undifferentiated progenitor cells that retain the capacity to both glial and neuronal lineages. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in stem cell fate determination and self-renewal. Our previous RNA-seq data indicated that the expression of miR-6216 was decreased in denervated hippocampal exosomes compared with normal. However, whether miR-6216 participates in regulating NSC function remains to be elucidated. In this study, we demonstrated that miR-6216 negatively regulates RAB6B expression. Forced overexpression of miR-6216 inhibited NSC proliferation, and overexpression of RAB6B promoted NSC proliferation. These findings suggest that miR-6216 played an important role in regulating NSC proliferation via targeting RAB6B, and improve the understanding of the miRNA-mRNA regulatory network that affects NSC proliferation.
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Affiliation(s)
- Wen Li
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Ruijie Ji
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Yujian Lin
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Xiang Cheng
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Zixin Tang
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Hui He
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Lei Zhang
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Jianbing Qin
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Meiling Tian
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Guohua Jin
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China
| | - Xinhua Zhang
- Department of Human Anatomy, Institute of Neurobiology, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China; Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, No.19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong 226001, Jiangsu, PR China.
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11
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Tan Z, Li W, Cheng X, Zhu Q, Zhang X. Non-Coding RNAs in the Regulation of Hippocampal Neurogenesis and Potential Treatment Targets for Related Disorders. Biomolecules 2022; 13:biom13010018. [PMID: 36671403 PMCID: PMC9855933 DOI: 10.3390/biom13010018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/17/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
Non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, circRNAs, and piRNAs, do not encode proteins. Nonetheless, they have critical roles in a variety of cellular activities-such as development, neurogenesis, degeneration, and the response to injury to the nervous system-via protein translation, RNA splicing, gene activation, silencing, modifications, and editing; thus, they may serve as potential targets for disease treatment. The activity of adult neural stem cells (NSCs) in the subgranular zone of the hippocampal dentate gyrus critically influences hippocampal function, including learning, memory, and emotion. ncRNAs have been shown to be involved in the regulation of hippocampal neurogenesis, including proliferation, differentiation, and migration of NSCs and synapse formation. The interaction among ncRNAs is complex and diverse and has become a major topic within the life science. This review outlines advances in research on the roles of ncRNAs in modulating NSC bioactivity in the hippocampus and discusses their potential applications in the treatment of illnesses affecting the hippocampus.
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Affiliation(s)
- Zhengye Tan
- Department of Anatomy, Institute of Neurobiology, Medical School, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Wen Li
- Department of Anatomy, Institute of Neurobiology, Medical School, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Xiang Cheng
- Department of Anatomy, Institute of Neurobiology, Medical School, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Qing Zhu
- School of Pharmacy, Nantong University, Nantong 226001, China
- Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, Nantong 226001, China
| | - Xinhua Zhang
- Department of Anatomy, Institute of Neurobiology, Medical School, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Central Lab, Yancheng Third People’s Hospital, The Sixth Affiliated Hospital of Nantong University, Yancheng 224001, China
- Correspondence:
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12
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Muacevic A, Adler JR, Cirino M, Trevisan FA, Peria F, Tirapelli D, Carlotti Jr CG. Modulation of Genes and MicroRNAs in the Neurospheres of Glioblastoma Cell Lines U343 and T98G Induced by Ionizing Radiation and Temozolomide Therapy. Cureus 2022; 14:e32211. [PMID: 36620850 PMCID: PMC9812005 DOI: 10.7759/cureus.32211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Glioblastoma is the most prevalent primary malignant neoplasm of the central nervous system. It has increased its incidence, while the overall survival remains over 14 months. PURPOSE The purpose is to evaluate the expression of the genes EGFR, PTEN, MGMT, and IDH1/2, and microRNAs miR-181b, miR-145, miR-149, and miR-128a in adhered cells (AC) and neurospheres (NS) from cell lines (T98G and U343) submitted to temozolomide (TMZ) and ionizing radiation (IR). METHODS T98G and U343 were treated with TMZ, IR, and TMZ+IR. The analysis of gene expression and miRNAs was performed using real-time PCR. RESULTS This study demonstrated: a) an improvement in the expression of IDH1 after IR and TMZ + IR in the NS (T98G); b) an increase in the expression of MGMT in NS (T98G) in IR groups and TMZ + IR. The expression of miRNAs results as a) AC (U343) expressed more miR-181b after TMZ, IR, and TMZ + IR; and miR-128a improved after TMZ, IR, and TMZ + IR; b) NS (T98G) after TMZ + IR expressed: miR-181b; miR-149; miR-145 and miR-128a; c) NS (U343) after IR huge expressed miR-149 and miR-145. CONCLUSION IR was an independent and determining radioresistance factor in NS. However, we observed no complementarity action of oncomiRs regulation.
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13
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Effects of the Targeted Regulation of CCRK by miR-335-5p on the Proliferation and Tumorigenicity of Human Renal Carcinoma Cells. JOURNAL OF ONCOLOGY 2022; 2022:2960050. [PMID: 36276294 PMCID: PMC9586783 DOI: 10.1155/2022/2960050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 07/23/2022] [Accepted: 07/28/2022] [Indexed: 12/24/2022]
Abstract
Cell cycle-related kinase (CCRK) is most closely related to cyclin-dependent protein kinase, which may activate cyclin-dependent kinase 2 and is associated with the growth of human cancer cells. However, the expression and function of CCRK in the pathogenesis of clear cell renal cell cancer (ccRCC) are unclear. Herein, this research aimed to explore the potential mechanism of the targeted regulation of CCRK by miR-335-5p on the proliferation and tumorigenicity of human ccRCC cells. The results showed that CCRK was significantly overexpressed in ccRCC tissues and cells, and knockdown of the CCRK expression by shRNA inhibited cell proliferation in vitro and in vivo and enhanced cell apoptosis in vitro, which indicated that CCRK could be a potential target for antitumour drugs in the treatment of ccRCC. Moreover, miR-335-5p was found to bind directly to the 3′ untranslated region of CCRK, was expressed at markedly low levels in ccRCC cells, and was closely associated with the tumour stage. The overexpression of CCRK partially reversed the inhibitory effects of miR-335-5p on the cell growth of ccRCC, which implied that miR-335-5p could serve as a promising tumour inhibitor for ccRCC. In summary, CCRK could serve as an alternative antitumour drug target, and miR-335-5p could be a promising therapeutic tumour inhibitor for ccRCC treatment.
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14
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Chan JNM, Sánchez-Vidaña DI, Anoopkumar-Dukie S, Li Y, Benson Wui-Man L. RNA-binding protein signaling in adult neurogenesis. Front Cell Dev Biol 2022; 10:982549. [PMID: 36187492 PMCID: PMC9523427 DOI: 10.3389/fcell.2022.982549] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/01/2022] [Indexed: 11/13/2022] Open
Abstract
The process of neurogenesis in the brain, including cell proliferation, differentiation, survival, and maturation, results in the formation of new functional neurons. During embryonic development, neurogenesis is crucial to produce neurons to establish the nervous system, but the process persists in certain brain regions during adulthood. In adult neurogenesis, the production of new neurons in the hippocampus is accomplished via the division of neural stem cells. Neurogenesis is regulated by multiple factors, including gene expression at a temporal scale and post-transcriptional modifications. RNA-binding Proteins (RBPs) are known as proteins that bind to either double- or single-stranded RNA in cells and form ribonucleoprotein complexes. The involvement of RBPs in neurogenesis is crucial for modulating gene expression changes and posttranscriptional processes. Since neurogenesis affects learning and memory, RBPs are closely associated with cognitive functions and emotions. However, the pathways of each RBP in adult neurogenesis remain elusive and not clear. In this review, we specifically summarize the involvement of several RBPs in adult neurogenesis, including CPEB3, FXR2, FMRP, HuR, HuD, Lin28, Msi1, Sam68, Stau1, Smaug2, and SOX2. To understand the role of these RBPs in neurogenesis, including cell proliferation, differentiation, survival, and maturation as well as posttranscriptional gene expression, we discussed the protein family, structure, expression, functional domain, and region of action. Therefore, this narrative review aims to provide a comprehensive overview of the RBPs, their function, and their role in the process of adult neurogenesis as well as to identify possible research directions on RBPs and neurogenesis.
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Affiliation(s)
- Jackie Ngai-Man Chan
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Dalinda Isabel Sánchez-Vidaña
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
- Mental Health Research Centre, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | | | - Yue Li
- State Key Laboratory of Component-Based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lau Benson Wui-Man
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
- Mental Health Research Centre, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
- *Correspondence: Lau Benson Wui-Man,
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15
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Chen X, Xie W, Zhang M, Shi Y, Xu S, Cheng H, Wu L, Pathak JL, Zheng Z. The Emerging Role of Non-Coding RNAs in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells. Front Cell Dev Biol 2022; 10:903278. [PMID: 35652090 PMCID: PMC9150698 DOI: 10.3389/fcell.2022.903278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 04/25/2022] [Indexed: 11/13/2022] Open
Abstract
Autologous bone marrow-derived mesenchymal stem cells (BMSCs) are more easily available and frequently used for bone regeneration in clinics. Osteogenic differentiation of BMSCs involves complex regulatory networks affecting bone formation phenomena. Non-coding RNAs (ncRNAs) refer to RNAs that do not encode proteins, mainly including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, transfer RNA-derived small RNAs, etc. Recent in vitro and in vivo studies had revealed the regulatory role of ncRNAs in osteogenic differentiation of BMSCs. NcRNAs had both stimulatory and inhibitory effects on osteogenic differentiation of BMSCs. During the physiological condition, osteo-stimulatory ncRNAs are upregulated and osteo-inhibitory ncRNAs are downregulated. The opposite effects might occur during bone degenerative disease conditions. Intracellular ncRNAs and ncRNAs from neighboring cells delivered via exosomes participate in the regulatory process of osteogenic differentiation of BMSCs. In this review, we summarize the recent advances in the regulatory role of ncRNAs on osteogenic differentiation of BMSCs during physiological and pathological conditions. We also discuss the prospects of the application of modulation of ncRNAs function in BMSCs to promote bone tissue regeneration in clinics.
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Affiliation(s)
- Xiaoying Chen
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Wei Xie
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Ming Zhang
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Yuhan Shi
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Shaofen Xu
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Haoyu Cheng
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Lihong Wu
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China.,Department of Basic Oral Medicine, School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou, China
| | - Janak L Pathak
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China.,Department of Basic Oral Medicine, School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou, China
| | - Zhichao Zheng
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China.,Department of Basic Oral Medicine, School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou, China.,Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
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16
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Zhao C, Xie W, Zhu H, Zhao M, Liu W, Wu Z, Wang L, Zhu B, Li S, Zhou Y, Jiang X, Xu Q, Ren C. LncRNAs and their RBPs: How to influence the fate of stem cells? Stem Cell Res Ther 2022; 13:175. [PMID: 35505438 PMCID: PMC9066789 DOI: 10.1186/s13287-022-02851-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 04/12/2022] [Indexed: 12/12/2022] Open
Abstract
Stem cells are distinctive cells that have self-renewal potential and unique ability to differentiate into multiple functional cells. Stem cell is a frontier field of life science research and has always been a hot spot in biomedical research. Recent studies have shown that long non-coding RNAs (lncRNAs) have irreplaceable roles in stem cell self-renewal and differentiation. LncRNAs play crucial roles in stem cells through a variety of regulatory mechanisms, including the recruitment of RNA-binding proteins (RBPs) to affect the stability of their mRNAs or the expression of downstream genes. RBPs interact with different RNAs to regulate gene expression at transcriptional and post-transcriptional levels and play important roles in determining the fate of stem cells. In this review, the functions of lncRNAs and their RBPs in self-renewal and differentiation of stem cell are summarized. We focus on the four regulatory mechanisms by which lncRNAs and their RBPs are involved in epigenetic regulation, signaling pathway regulation, splicing, mRNA stability and subcellular localization and further discuss other noncoding RNAs (ncRNAs) and their RBPs in the fate of stem cells. This work provides a more comprehensive understanding of the roles of lncRNAs in determining the fate of stem cells, and a further understanding of their regulatory mechanisms will provide a theoretical basis for the development of clinical regenerative medicine.
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Affiliation(s)
- Cong Zhao
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Wen Xie
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Hecheng Zhu
- Changsha Kexin Cancer Hospital, Changsha, 410205, China
| | - Ming Zhao
- Changsha Kexin Cancer Hospital, Changsha, 410205, China
| | - Weidong Liu
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Zhaoping Wu
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Lei Wang
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Bin Zhu
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Shasha Li
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Yao Zhou
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Xingjun Jiang
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. .,Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Qiang Xu
- Department of Orthopedics, The Affiliated Zhuzhou Hospital of Xiangya Medical College, Central South University, Zhuzhou, 412007, China. .,School of Materials Science and Engineering, Central South University, Changsha, 410083, China.
| | - Caiping Ren
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. .,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China.
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17
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Shimizu S, Maeda N, Takahashi Y, Uomoto S, Takesue K, Ojiro R, Tang Q, Ozawa S, Okano H, Takashima K, Woo GH, Yoshida T, Shibutani M. Oral exposure to aluminum chloride for 28 days suppresses neural stem cell proliferation and increases mature granule cells in adult hippocampal neurogenesis of young-adult rats. J Appl Toxicol 2022; 42:1337-1353. [PMID: 35146777 DOI: 10.1002/jat.4299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/31/2022] [Accepted: 02/07/2022] [Indexed: 11/06/2022]
Abstract
Aluminum (Al), a common light metal, affects the developing nervous system. Developmental exposure to Al chloride (AlCl3 ) induces aberrant neurogenesis by targeting neural stem cells (NSCs) and/or neural progenitor cells (NPCs) in the dentate gyrus (DG) of rats and mice. To investigate whether hippocampal neurogenesis is similarly affected by AlCl3 exposure in a general toxicity study, AlCl3 was orally administered to 5-week-old Sprague Dawley rats at dosages of 0, 4000, or 8000 ppm in drinking water for 28 days. AlCl3 downregulated Sox2 transcript levels in the DG at the highest dosage and produced a dose-dependent decrease of SOX2+ cells without altering numbers of GFAP+ or TBR2+ cells in the subgranular zone, suggesting that AlCl3 decreases Type 2a NPCs. High-dose exposure downregulated Pcna, upregulated Pvalb, and altered expression of genes suggestive of oxidative stress induction (upregulation of Nos2 and downregulation of antioxidant enzyme genes), indicating suppressed proliferation and differentiation of Type 1 NSCs. AlCl3 doses also increased mature granule cells in the DG. Upregulation of Reln may have contributed to an increase of granule cells to compensate for the decrease of Type 2a NPCs. Moreover, upregulation of Calb2, Gria2, Mapk3, and Tgfb3, as well as increased numbers of activated astrocytes in the DG hilus, may represent ameliorating responses against suppressed neurogenesis. These results suggest that 28-day exposure of young-adult rats to AlCl3 differentially targeted NPCs and mature granule cells in hippocampal neurogenesis, yielding a different pattern of disrupted neurogenesis from developmental exposure.
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Affiliation(s)
- Saori Shimizu
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Natsuno Maeda
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Yasunori Takahashi
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Suzuka Uomoto
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Keisuke Takesue
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Ryota Ojiro
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Qian Tang
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Shunsuke Ozawa
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Hiromu Okano
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Kazumi Takashima
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Gye-Hyeong Woo
- Laboratory of Histopathology, Department of Clinical Laboratory Science, Semyung University, Jecheon-si, Chungbuk, Republic of Korea
| | - Toshinori Yoshida
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
| | - Makoto Shibutani
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.,Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
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18
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Nsengimana B, Khan FA, Ngowi EE, Zhou X, Jin Y, Jia Y, Wei W, Ji S. Processing body (P-body) and its mediators in cancer. Mol Cell Biochem 2022; 477:1217-1238. [PMID: 35089528 DOI: 10.1007/s11010-022-04359-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 01/11/2022] [Indexed: 12/24/2022]
Abstract
In recent years, processing bodies (P-bodies) formed by liquid-liquid phase separation, have attracted growing scientific attention due to their involvement in numerous cellular activities, including the regulation of mRNAs decay or storage. These cytoplasmic dynamic membraneless granules contain mRNA storage and decay components such as deadenylase and decapping factors. In addition, different mRNA metabolic regulators, including m6A readers and gene-mediated miRNA-silencing, are also associated with such P-bodies. Cancerous cells may profit from these mRNA decay shredders by up-regulating the expression level of oncogenes and down-regulating tumor suppressor genes. The main challenges of cancer treatment are drug resistance, metastasis, and cancer relapse likely associated with cancer stem cells, heterogeneity, and plasticity features of different tumors. The mRNA metabolic regulators based on P-bodies play a great role in cancer development and progression. The dysregulation of P-bodies mediators affects mRNA metabolism. However, less is known about the relationship between P-bodies mediators and cancerous behavior. The current review summarizes the recent studies on P-bodies mediators, their contribution to tumor development, and their potential in the clinical setting, particularly highlighting the P-bodies as potential drug-carriers such as exosomes to anticancer in the future.
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Affiliation(s)
- Bernard Nsengimana
- Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Henan, 475004, People's Republic of China
| | - Faiz Ali Khan
- Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Henan, 475004, People's Republic of China
| | - Ebenezeri Erasto Ngowi
- Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Henan, 475004, People's Republic of China
| | - Xuefeng Zhou
- Department of Oncology, Dongtai Affiliated Hospital of Nantong University, Dongtai, 224200, Jiangsu, People's Republic of China
| | - Yu Jin
- Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Henan, 475004, People's Republic of China
| | - Yuting Jia
- Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Henan, 475004, People's Republic of China
| | - Wenqiang Wei
- Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Henan, 475004, People's Republic of China.
| | - Shaoping Ji
- Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Henan, 475004, People's Republic of China.
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19
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Zheng Z, Chen J, Chopp M. Mechanisms of Plasticity Remodeling and Recovery. Stroke 2022. [DOI: 10.1016/b978-0-323-69424-7.00011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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20
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Uzuner E, Ulu GT, Gürler SB, Baran Y. The Role of MiRNA in Cancer: Pathogenesis, Diagnosis, and Treatment. Methods Mol Biol 2022; 2257:375-422. [PMID: 34432288 DOI: 10.1007/978-1-0716-1170-8_18] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cancer is also determined by the alterations of oncogenes and tumor suppressor genes. These gene expressions can be regulated by microRNAs (miRNA). At this point, researchers focus on addressing two main questions: "How are oncogenes and/or tumor suppressor genes regulated by miRNAs?" and "Which other mechanisms in cancer cells are regulated by miRNAs?" In this work we focus on gathering the publications answering these questions. The expression of miRNAs is affected by amplification, deletion or mutation. These processes are controlled by oncogenes and tumor suppressor genes, which regulate different mechanisms of cancer initiation and progression including cell proliferation, cell growth, apoptosis, DNA repair, invasion, angiogenesis, metastasis, drug resistance, metabolic regulation, and immune response regulation in cancer cells. In addition, profiling of miRNA is an important step in developing a new therapeutic approach for cancer.
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Affiliation(s)
- Erez Uzuner
- Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey
| | - Gizem Tugçe Ulu
- Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey
| | - Sevim Beyza Gürler
- Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey
| | - Yusuf Baran
- Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey.
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21
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Soni N, Gupta S, Rawat S, Krishnakumar V, Mohanty S, Banerjee A. MicroRNA-Enriched Exosomes from Different Sources of Mesenchymal Stem Cells Can Differentially Modulate Functions of Immune Cells and Neurogenesis. Biomedicines 2021; 10:biomedicines10010069. [PMID: 35052749 PMCID: PMC8772751 DOI: 10.3390/biomedicines10010069] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/02/2021] [Accepted: 12/02/2021] [Indexed: 01/10/2023] Open
Abstract
Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells.
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Affiliation(s)
- Naina Soni
- Laboratory of Virology, Regional Centre for Biotechnology, Faridabad 121001, India; (N.S.); (S.R.)
| | - Suchi Gupta
- DBT-Centre of Excellence for Stem Cell Research, Stem Cell Facility, All India Institute of Medical Sciences, New Delhi 110029, India; (S.G.); (V.K.)
| | - Surender Rawat
- Laboratory of Virology, Regional Centre for Biotechnology, Faridabad 121001, India; (N.S.); (S.R.)
| | - Vishnu Krishnakumar
- DBT-Centre of Excellence for Stem Cell Research, Stem Cell Facility, All India Institute of Medical Sciences, New Delhi 110029, India; (S.G.); (V.K.)
| | - Sujata Mohanty
- DBT-Centre of Excellence for Stem Cell Research, Stem Cell Facility, All India Institute of Medical Sciences, New Delhi 110029, India; (S.G.); (V.K.)
- Correspondence: (S.M.); (A.B.)
| | - Arup Banerjee
- Laboratory of Virology, Regional Centre for Biotechnology, Faridabad 121001, India; (N.S.); (S.R.)
- Correspondence: (S.M.); (A.B.)
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22
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Liu Q, Tian R, Yu P, Shu M. miR-221/222 suppression induced by activation of the cAMP/PKA/CREB1 pathway is required for cAMP-induced bidirectional differentiation of glioma cells. FEBS Lett 2021; 595:2829-2843. [PMID: 34687039 DOI: 10.1002/1873-3468.14208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/30/2021] [Accepted: 08/30/2021] [Indexed: 12/29/2022]
Abstract
Factors that increase cAMP levels can induce lineage-specific differentiation of glioma cells into astrocyte-like cells. However, the differentiation pattern and underlying mechanisms remain unclear. Here, we find that cAMP/protein kinase A (PKA)/cAMP responsive element binding protein 1 (CREB1)-induced miR-221/222 suppression contributes to the neuron-like differentiation of gliomas. cAMP agonists selectively induced neuron- and astrocyte-like but not oligodendrocyte-like differentiation of C6 glioma cells. PKA inhibitors and CREB1 knockout blocked neuron-like differentiation of glioma cells. cAMP inhibited miR-221/222 in a PKA/CREB1-dependent manner. Importantly, both in vitro and in vivo assays demonstrated that transcriptional suppression of miR-221/222 is required for neuronal differentiation of glioma cells. Our findings suggest that increasing cAMP levels can induce bidirectional differentiation of glioma cells. Furthermore, the miR-221/222 cluster acts as an epigenetic brake during glioma differentiation.
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Affiliation(s)
- Qian Liu
- Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ruotong Tian
- Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Panpan Yu
- Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Minfeng Shu
- Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
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23
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German OL, Vallese-Maurizi H, Soto TB, Rotstein NP, Politi LE. Retina stem cells, hopes and obstacles. World J Stem Cells 2021; 13:1446-1479. [PMID: 34786153 PMCID: PMC8567457 DOI: 10.4252/wjsc.v13.i10.1446] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/14/2021] [Accepted: 09/17/2021] [Indexed: 02/07/2023] Open
Abstract
Retinal degeneration is a major contributor to visual dysfunction worldwide. Although it comprises several eye diseases, loss of retinal pigment epithelial (RPE) and photoreceptor cells are the major contributors to their pathogenesis. Early therapies included diverse treatments, such as provision of anti-vascular endothelial growth factor and many survival and trophic factors that, in some cases, slow down the progression of the degeneration, but do not effectively prevent it. The finding of stem cells (SC) in the eye has led to the proposal of cell replacement strategies for retina degeneration. Therapies using different types of SC, such as retinal progenitor cells (RPCs), embryonic SC, pluripotent SCs (PSCs), induced PSCs (iPSCs), and mesenchymal stromal cells, capable of self-renewal and of differentiating into multiple cell types, have gained ample support. Numerous preclinical studies have assessed transplantation of SC in animal models, with encouraging results. The aim of this work is to revise the different preclinical and clinical approaches, analyzing the SC type used, their efficacy, safety, cell attachment and integration, absence of tumor formation and immunorejection, in order to establish which were the most relevant and successful. In addition, we examine the questions and concerns still open in the field. The data demonstrate the existence of two main approaches, aimed at replacing either RPE cells or photoreceptors. Emerging evidence suggests that RPCs and iPSC are the best candidates, presenting no ethical concerns and a low risk of immunorejection. Clinical trials have already supported the safety and efficacy of SC treatments. Serious concerns are pending, such as the risk of tumor formation, lack of attachment or integration of transplanted cells into host retinas, immunorejection, cell death, and also ethical. However, the amazing progress in the field in the last few years makes it possible to envisage safe and effective treatments to restore vision loss in a near future.
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Affiliation(s)
- Olga L German
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, Bahia blanca 8000, Buenos Aires, Argentina
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Bahía Blanca 8000, Buenos Aires, Argentina
| | - Harmonie Vallese-Maurizi
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, Bahia blanca 8000, Buenos Aires, Argentina
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Bahía Blanca 8000, Buenos Aires, Argentina
| | - Tamara B Soto
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Bahía Blanca 8000, Buenos Aires, Argentina
| | - Nora P Rotstein
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, Bahia blanca 8000, Buenos Aires, Argentina
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Bahía Blanca 8000, Buenos Aires, Argentina
| | - Luis Enrique Politi
- Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Bahía Blanca 8000, Buenos Aires, Argentina
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24
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Chen Z, Huang Y, Yu C, Liu Q, Qiu C, Wan G. Cochlear Sox2 + Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules. Front Cell Dev Biol 2021; 9:728352. [PMID: 34621745 PMCID: PMC8490772 DOI: 10.3389/fcell.2021.728352] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/30/2021] [Indexed: 12/13/2022] Open
Abstract
In the mammalian cochlea, spiral ganglion neurons (SGNs) relay the acoustic information to the central auditory circuits. Degeneration of SGNs is a major cause of sensorineural hearing loss and severely affects the effectiveness of cochlear implant therapy. Cochlear glial cells are able to form spheres and differentiate into neurons in vitro. However, the identity of these progenitor cells is elusive, and it is unclear how to differentiate these cells toward functional SGNs. In this study, we found that Sox2+ subpopulation of cochlear glial cells preserves high potency of neuronal differentiation. Interestingly, Sox2 expression was downregulated during neuronal differentiation and Sox2 overexpression paradoxically inhibited neuronal differentiation. Our data suggest that Sox2+ glial cells are potent SGN progenitor cells, a phenotype independent of Sox2 expression. Furthermore, we identified a combination of small molecules that not only promoted neuronal differentiation of Sox2– glial cells, but also removed glial cell identity and promoted the maturation of the induced neurons (iNs) toward SGN fate. In summary, we identified Sox2+ glial subpopulation with high neuronal potency and small molecules inducing neuronal differentiation toward SGNs.
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Affiliation(s)
- Zhen Chen
- MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China
| | - Yuhang Huang
- MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China
| | - Chaorong Yu
- MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China
| | - Qing Liu
- MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China
| | - Cui Qiu
- MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China
| | - Guoqiang Wan
- MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.,Research Institute of Otolaryngology, Nanjing, China.,Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.,Institute for Brain Sciences, Nanjing University, Nanjing, China
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25
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Aoki A, Aoki R, Yatagai M, Kawasumi T. Comparative analysis of microRNA expression profiles in the colons of specific pathogen-free mice and germ-free mice. Biosci Biotechnol Biochem 2021; 85:1869-1872. [PMID: 34263295 DOI: 10.1093/bbb/zbab112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/13/2021] [Indexed: 11/13/2022]
Abstract
MicroRNAs play an important role in microbiota-host crosstalk. In this study, we compared microRNA expression in whole colons of specific pathogen-free mice and germ-free mice. Forty-eight microRNAs were differentially expressed by more than 2-fold. Gene ontology analysis of the predicted mRNA targets revealed that the majority of the most significant gene ontology terms were related to GTPases and nerves.
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Affiliation(s)
- Ayako Aoki
- Department of Food and Nutrition, Faculty of Human Sciences and Design, Japan Women's University, Bunkyo-ku, Tokyo, Japan.,NARO Institute of Livestock and Grassland Science, Tsukuba, Ibaraki, Japan
| | - Reiji Aoki
- NARO Institute of Livestock and Grassland Science, Tsukuba, Ibaraki, Japan
| | - Madoka Yatagai
- Department of Food and Nutrition, Faculty of Human Sciences and Design, Japan Women's University, Bunkyo-ku, Tokyo, Japan
| | - Toshiyuki Kawasumi
- Department of Food and Nutrition, Faculty of Human Sciences and Design, Japan Women's University, Bunkyo-ku, Tokyo, Japan
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26
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let-7 microRNAs: Their Role in Cerebral and Cardiovascular Diseases, Inflammation, Cancer, and Their Regulation. Biomedicines 2021; 9:biomedicines9060606. [PMID: 34073513 PMCID: PMC8227213 DOI: 10.3390/biomedicines9060606] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 12/14/2022] Open
Abstract
The let-7 family is among the first microRNAs found. Recent investigations have indicated that it is highly expressed in many systems, including cerebral and cardiovascular systems. Numerous studies have implicated the aberrant expression of let-7 members in cardiovascular diseases, such as stroke, myocardial infarction (MI), cardiac fibrosis, and atherosclerosis as well as in the inflammation related to these diseases. Furthermore, the let-7 microRNAs are involved in development and differentiation of embryonic stem cells in the cardiovascular system. Numerous genes have been identified as target genes of let-7, as well as a number of the let-7’ regulators. Further studies are necessary to identify the gene targets and signaling pathways of let-7 in cardiovascular diseases and inflammatory processes. The bulk of the let-7’ regulatory proteins are well studied in development, proliferation, differentiation, and cancer, but their roles in inflammation, cardiovascular diseases, and/or stroke are not well understood. Further knowledge on the regulation of let-7 is crucial for therapeutic advances. This review focuses on research progress regarding the roles of let-7 and their regulation in cerebral and cardiovascular diseases and associated inflammation.
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27
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Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis. Int J Mol Sci 2021; 22:ijms22084290. [PMID: 33924260 PMCID: PMC8074756 DOI: 10.3390/ijms22084290] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 04/15/2021] [Accepted: 04/15/2021] [Indexed: 12/11/2022] Open
Abstract
The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.
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28
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Stevanovic M, Drakulic D, Lazic A, Ninkovic DS, Schwirtlich M, Mojsin M. SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis. Front Mol Neurosci 2021; 14:654031. [PMID: 33867936 PMCID: PMC8044450 DOI: 10.3389/fnmol.2021.654031] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 03/11/2021] [Indexed: 12/11/2022] Open
Abstract
The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.
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Affiliation(s)
- Milena Stevanovic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.,Faculty of Biology, University of Belgrade, Belgrade, Serbia.,Serbian Academy of Sciences and Arts, Belgrade, Serbia
| | - Danijela Drakulic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Andrijana Lazic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Danijela Stanisavljevic Ninkovic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Marija Schwirtlich
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Marija Mojsin
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
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29
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Luo J, Zou H, Deng L, Sun X, Yuan P, Li P. Lin28 Inhibits the Differentiation from Mouse Embryonic Stem Cells to Glial Lineage Cells through Upregulation of Yap1. Stem Cells Int 2021; 2021:6674283. [PMID: 33688355 PMCID: PMC7920735 DOI: 10.1155/2021/6674283] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/05/2021] [Accepted: 02/10/2021] [Indexed: 02/07/2023] Open
Abstract
The RNA-binding protein Lin28 regulates neurogliogenesis in mammals, independently of the let-7 microRNA. However, the detailed regulatory mechanism remains obscured. Here, we established Lin28a or Lin28b overexpression mouse embryonic stem cells (ESCs) and found that these cells expressed similar levels of the core pluripotent factors, such as Oct4 and Sox2, and increased Yap1 but decreased lineage-specific markers compared to the control ESCs. Further differentiation of these ESCs to neuronal and glial lineage cells revealed that Lin28a/b overexpression did not affect the expression of neuronal marker βIII-tubulin, but dramatically inhibited the glial lineage markers, such as Gfap and Mbp. Interestingly, overexpression of Yap1 in mouse ESCs phenocopied Lin28a/b overexpression ESCs by showing defect in glial cell differentiation. Inhibition of Yap1/Tead-mediated transcription with verteporfin partially rescued the differentiation defect of Lin28a/b overexpression ESCs. Mechanistically, we demonstrated that Lin28 can directly bind to Yap1 mRNA, and the induction of Yap1 by Lin28a in mESCs is independent of Let7. Taken together, our results unravel a novel Lin28-Yap1 regulatory axis during mESC to glial lineage cell differentiation, which may shed light on glial cell generation in vitro.
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Affiliation(s)
- Juan Luo
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
| | - Hailin Zou
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
| | - Liang Deng
- Department of General Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
| | - Xiang Sun
- Department of Medical Bioinformatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510275, China
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China
| | - Ping Yuan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong 510655, China
| | - Peng Li
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
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30
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Jiang T, Hu S, Dai S, Yi Y, Wang T, Li X, Luo M, Li K, Chen L, Wang H, Xu D. Programming changes of hippocampal miR-134-5p/SOX2 signal mediate the susceptibility to depression in prenatal dexamethasone-exposed female offspring. Cell Biol Toxicol 2021; 38:69-86. [PMID: 33619658 DOI: 10.1007/s10565-021-09590-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 02/09/2021] [Indexed: 12/21/2022]
Abstract
Depression is a neuropsychiatric disorder and has intrauterine developmental origins. This study aimed to confirm the depression susceptibility in offspring rats induced by prenatal dexamethasone exposure (PDE) and to further explore the intrauterine programming mechanism. Wistar rats were injected with dexamethasone (0.2 mg/kg·d) subcutaneously during the gestational days 9-20 and part of the offspring was given chronic stress at postnatal weeks 10-12. Behavioral results showed that the adult PDE female offspring was susceptible to depression, accompanied by increased hippocampal miR-134-5p expression and decreased sex-determining region Y-box 2 (SOX2) expression, as well as disorders of neural progenitor cells proliferation and hippocampal neurogenesis. The PDE female fetal rats presented consistent changes with the adult offspring, accompanied by the upregulation of glucocorticoid receptor (GR) expression and decreased sirtuin 1 (SIRT1) expression. We further found that the H3K9ac level of the miR-134-5p promoter was significantly increased in the PDE fetal hippocampus, as well as in adult offspring before and after chronic stress. In vitro, the changes of GR/SIRT1/miR-134-5p/SOX2 signal by dexamethasone were consistent with in vivo experiments, which could be reversed by GR receptor antagonist, SIRT1 agonist, and miR-134-5p inhibitor. This study confirmed that PDE led to an increased expression level as well as H3K9ac level of miR-134-5p by activating the GR/SIRT1 pathway in the fetal hippocampus and then inhibited the SOX2 expression. The programming effect mediated by the abnormal epigenetic modification could last from intrauterine to adulthood, which constitutes the intrauterine programming mechanism leading to hippocampal neurogenesis disorders and depression susceptibility in female offspring. Intrauterine programming mechanism for the increased depressive susceptibility in adult female offspring by prenatal dexamethasone exposure (PDE). GR, glucocorticoid receptor; SIRT1, sirtuin 1; SOX2, sex-determining region Y-box 2; NPCs, neuroprogenitor cells; H3K9ac, histone 3 lysine 9 acetylation; GRE, glucocorticoid response element.
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Affiliation(s)
- Tao Jiang
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China
| | - Shuwei Hu
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China
| | - Shiyun Dai
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China
| | - Yiwen Yi
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China
| | - Tingting Wang
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China
| | - Xufeng Li
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China
| | - Mingcui Luo
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China
| | - Ke Li
- Demonstration Center for Experimental Basic Medicine Education, Wuhan University, Wuhan, 430071, China
| | - Liaobin Chen
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hui Wang
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China.,Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China
| | - Dan Xu
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China. .,Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China.
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31
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Yang B, Zang L, Cui J, Wei L. Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction. Stem Cell Res Ther 2021; 12:125. [PMID: 33579365 PMCID: PMC7881478 DOI: 10.1186/s13287-021-02187-y] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 01/24/2021] [Indexed: 12/13/2022] Open
Abstract
Background Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. Methods The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. Results Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and β-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. Conclusion Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.
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Affiliation(s)
- Bo Yang
- Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China
| | - Li'e Zang
- Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China
| | - Jingwen Cui
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China
| | - Linlin Wei
- Department of Gynaecology, The First Affiliated Hospital of Jinzhou Medical University, No.2, Section 5, Renmin Street, Jinzhou, Liaoning Province, China.
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Zhou Y, Yang L, Bo C, Zhang X, Zhang J, Li Y. MicroRNA-9-3p Aggravates Cerebral Ischemia/Reperfusion Injury by Targeting Fibroblast Growth Factor 19 (FGF19) to Inactivate GSK-3β/Nrf2/ARE Signaling. Neuropsychiatr Dis Treat 2021; 17:1989-2002. [PMID: 34177264 PMCID: PMC8219303 DOI: 10.2147/ndt.s290237] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 04/27/2021] [Indexed: 12/25/2022] Open
Abstract
PURPOSE MicroRNAs (miRNAs) are emerging as essential regulators in the development of cerebral ischemia/reperfusion (I/R) injury. This study aimed to explore the regulation of miR-9-3p on FGF19-GSK-3β/Nrf2/ARE signaling in cerebral I/R injury. MATERIALS AND METHODS A mouse model with I/R injury was constructed by middle cerebral artery occlusion (MCAO) and an HT22 cell model was established by oxygen-glucose deprivation/reperfusion (OGD/R). The expression of miR-9-3p was detected by RT-qPCR. Protein expression of fibroblast growth factor 19 (FGF19), cleaved caspase-3, and GSK-3β signaling-related proteins (p-GSK-3β and Nrf2) were detected by Western blot. Cell viability was assessed by MTT assay. Oxidative stress was detected by commercial kits. The target of miR-9-3p was predicted by TargetScan and confirmed by luciferase reporter assay. The effects of miR-9-3p on GSK-3β/Nrf2/ARE signaling were assessed by rescue experiments. RESULTS MiR-9-3p was significantly upregulated in brain tissues of MCAO/R-treated mice and OGD/R-treated HT22 cells. Downregulation of miR-9-3p attenuated infarct volume and neurological outcomes of MCAO/R-treated mice in vivo and OGD/R-induced cell injury and oxidative stress in vitro, while overexpression of miR-9-3p showed the opposite effects. MiR-9-3p directly bound to the 3'-untranslated region of FGF19 and negatively regulated its expression. Inhibition of miR-9-3p enhanced GSK-3β/Nrf2/ARE signaling-mediated antioxidant response, while this effect was partially eliminated by FGF19 or Nrf2 silencing. CONCLUSION Our study suggests that inhibition of miR-9-3p protects against cerebral I/R injury through activating GSK-3β/Nrf2/ARE signaling-mediated antioxidant responses by targeting FGF19, providing a potential therapeutic target for ischemic stroke.
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Affiliation(s)
- Yadong Zhou
- Department of Emergency, The Second Affiliated Hospital of Shandong First Medical University, Taian City, Shandong Province, People's Republic of China
| | - Lin Yang
- Department of Hospital Infection Management, The Second Affiliated Hospital of Shandong First Medical University, Taian City, Shandong Province, People's Republic of China
| | - Chu Bo
- Department of Emergency, Taian City Central Hospital, Taian City, Shandong Province, People's Republic of China
| | - Xianjing Zhang
- Department of Emergency, The Second Affiliated Hospital of Shandong First Medical University, Taian City, Shandong Province, People's Republic of China
| | - Junli Zhang
- Department of Emergency, The Second Affiliated Hospital of Shandong First Medical University, Taian City, Shandong Province, People's Republic of China
| | - Yun Li
- Department of Emergency, Jinan Central Hospital, Jinan City, Shandong Province, People's Republic of China
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Abstract
BACKGROUND MicroRNA 221 has been found to be a good marker for several cancers. Some studies also focused on the relationship between microRNA 221 and glioma. However, the results are controversial. We aimed to systematically evaluate the prognostic role of microRNA 221 in glioma through performing a meta-analysis. METHODS The articles which were included in our study were searched on the Web of Science, EMBASE, PubMed, Cochrane Library and China National Knowledge Infrastructure. The basic characteristics and relevant data were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to evaluate the prognostic role of microRNA 221 in glioma. RESULTS Eight studies with 1069 patients were included. We systematically evaluated the role of microRNA 221 for overall survival (OS) and disease free survival (DFS) in glioma patients (HR for OS = 1.66, 95% CI, 1.34-2.04; HR for DFS = 1.14, 95% CI, 1.02-1.26). Subgroup analyses were performed according to the nation of the studies, the origin of the samples, the stage of the tumors, the cut-off value, and the method for detecting the microRNA 221. No significant publication bias was found (P = .133). CONCLUSION In conclusion, high expression of microRNA 221 was related to poor prognosis of glioma. These findings may assist future exploration on microRNA 221 and help predict the prognosis of glioma. However, due to the significant heterogeneity of these studies, more studies are warranted.
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Affiliation(s)
- Yanlin Song
- Department of Neurosurgery and National Clinical Research Center for Geriatrics
- Department of Biotherapy and Cancer Center
| | - Min He
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Jing Zhang
- Department of Neurosurgery and National Clinical Research Center for Geriatrics
| | - Jianguo Xu
- Department of Neurosurgery and National Clinical Research Center for Geriatrics
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Losurdo M, Grilli M. Extracellular Vesicles, Influential Players of Intercellular Communication within Adult Neurogenic Niches. Int J Mol Sci 2020; 21:E8819. [PMID: 33233420 PMCID: PMC7700666 DOI: 10.3390/ijms21228819] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/18/2020] [Accepted: 11/19/2020] [Indexed: 12/14/2022] Open
Abstract
Adult neurogenesis, involving the generation of functional neurons from adult neural stem cells (NSCs), occurs constitutively in discrete brain regions such as hippocampus, sub-ventricular zone (SVZ) and hypothalamus. The intrinsic structural plasticity of the neurogenic process allows the adult brain to face the continuously changing external and internal environment and requires coordinated interplay between all cell types within the specialized microenvironment of the neurogenic niche. NSC-, neuronal- and glia-derived factors, originating locally, regulate the balance between quiescence and self-renewal of NSC, their differentiation programs and the survival and integration of newborn cells. Extracellular Vesicles (EVs) are emerging as important mediators of cell-to-cell communication, representing an efficient way to transfer the biologically active cargos (nucleic acids, proteins, lipids) by which they modulate the function of the recipient cells. Current knowledge of the physiological role of EVs within adult neurogenic niches is rather limited. In this review, we will summarize and discuss EV-based cross-talk within adult neurogenic niches and postulate how EVs might play a critical role in the regulation of the neurogenic process.
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Affiliation(s)
| | - Mariagrazia Grilli
- Laboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy;
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Madsen SD, Giler MK, Bunnell BA, O'Connor KC. Illuminating the Regenerative Properties of Stem Cells In Vivo with Bioluminescence Imaging. Biotechnol J 2020; 16:e2000248. [PMID: 33089922 DOI: 10.1002/biot.202000248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/17/2020] [Indexed: 11/10/2022]
Abstract
Preclinical animal studies are essential to the development of safe and effective stem cell therapies. Bioluminescence imaging (BLI) is a powerful tool in animal studies that enables the real-time longitudinal monitoring of stem cells in vivo to elucidate their regenerative properties. This review describes the application of BLI in preclinical stem cell research to address critical challenges in producing successful stem cell therapeutics. These challenges include stem cell survival, proliferation, homing, stress response, and differentiation. The applications presented here utilize bioluminescence to investigate a variety of stem and progenitor cells in several different in vivo models of disease and implantation. An overview of luciferase reporters is provided, along with the advantages and disadvantages of BLI. Additionally, BLI is compared to other preclinical imaging modalities and potential future applications of this technology are discussed in emerging areas of stem cell research.
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Affiliation(s)
- Sean D Madsen
- Department of Chemical and Biomolecular Engineering, School of Science and Engineering, Tulane University, New Orleans, LA, 70118, USA.,Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, New Orleans, LA, 70112, USA
| | - Margaret K Giler
- Department of Chemical and Biomolecular Engineering, School of Science and Engineering, Tulane University, New Orleans, LA, 70118, USA.,Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, New Orleans, LA, 70112, USA
| | - Bruce A Bunnell
- Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, New Orleans, LA, 70112, USA.,Department of Pharmacology, School of Medicine, Tulane University, New Orleans, LA, USA
| | - Kim C O'Connor
- Department of Chemical and Biomolecular Engineering, School of Science and Engineering, Tulane University, New Orleans, LA, 70118, USA.,Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, New Orleans, LA, 70112, USA
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Garrudo FFF, Mikael PE, Rodrigues CAV, Udangawa RW, Paradiso P, Chapman CA, Hoffman P, Colaço R, Cabral JMS, Morgado J, Linhardt RJ, Ferreira FC. Polyaniline-polycaprolactone fibers for neural applications: Electroconductivity enhanced by pseudo-doping. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 120:111680. [PMID: 33545842 DOI: 10.1016/j.msec.2020.111680] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 10/21/2020] [Accepted: 10/22/2020] [Indexed: 12/15/2022]
Abstract
Replenishing neurons in patients with neurodegenerative diseases is one of the ultimate therapies for these progressive, debilitating and fatal diseases. Electrical stimulation can improve neuron stem cell differentiation but requires a reliable nanopatterned electroconductive substrate. Potential candidate substrates are polycaprolactone (PCL) - polyaniline:camphorsulfonic acid (PANI:CSA) nanofibers, but their nanobiophysical properties need to be finetuned. The present study investigates the use of the pseudo-doping effect on the optimization of the electroconductivity of these polyaniline-based electrospun nanofibers. This was performed by developing a new solvent system that comprises a mixture of hexafluoropropanol (HFP) and trifluoroethanol (TFE). For the first time, an electroconductivity so high as 0.2 S cm-1 was obtained for, obtained from a TFE:HFP 50/50 vol% solution, while maintaining fiber biocompatibility. The physicochemical mechanisms behind these changes were studied. The results suggest HFP promotes changes on PANI chains conformations through pseudo-doping, leading to the observed enhancement in electroconductivity. The consequences of such change in the nanofabrication of PCL-PANI fibers include an increase in fiber diameter (373 ± 172 nm), a decrease in contact angle (42 ± 3°) and a decrease in Young modulus (1.6 ± 0.5 MPa), making these fibers interesting candidates for neural tissue engineering. Electrical stimulation of differentiating neural stem cells was performed using AC electrical current. Positive effects on cell alignment and gene expression (DCX, MAP2) are observed. The novel optimized platform shows promising applications for (1) building in vitro platforms for drug screening, (2) interfaces for deep-brain electrodes; and (3) fully grown and functional neurons transplantation.
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Affiliation(s)
- Fábio F F Garrudo
- Department of Chemistry and Chemical Biology, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USA; Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, Portugal; Department of Bioengineering and Instituto de Telecomunicações, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
| | - Paiyz E Mikael
- Department of Chemistry and Chemical Biology, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USA
| | - Carlos A V Rodrigues
- Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, Portugal
| | - Ranodhi W Udangawa
- Department of Chemistry and Chemical Biology, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USA
| | - Patrizia Paradiso
- IDMEC - Instituto de Engenharia Mecânica, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
| | - Caitlyn A Chapman
- Department of Chemistry and Chemical Biology, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USA
| | - Pauline Hoffman
- Department of Chemistry and Chemical Biology, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USA
| | - Rogério Colaço
- IDMEC - Instituto de Engenharia Mecânica, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
| | - Joaquim M S Cabral
- Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, Portugal
| | - Jorge Morgado
- Department of Bioengineering and Instituto de Telecomunicações, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
| | - Robert J Linhardt
- Department of Chemistry and Chemical Biology, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USA.
| | - Frederico Castelo Ferreira
- Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, Portugal.
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The roles of MicroRNAs in neural regenerative medicine. Exp Neurol 2020; 332:113394. [DOI: 10.1016/j.expneurol.2020.113394] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/15/2020] [Accepted: 06/25/2020] [Indexed: 12/22/2022]
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Zhang Y, Wu Z, Li X, Wan Y, Zhang Y, Zhao P. Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1. Stem Cell Res Ther 2020; 11:423. [PMID: 32993796 PMCID: PMC7523391 DOI: 10.1186/s13287-020-01936-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/28/2020] [Accepted: 09/15/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Currently, numerous animal studies have shown that exposure to commonly used general anesthetics during pregnancy may cause neurocognitive impairment in the offspring. Reportedly, exposure to sevoflurane during mid-trimester of pregnancy can inhibit proliferation of neural stem cells (NSCs) and lead to early apoptosis. Whether exposure to sevoflurane during pregnancy affects the differentiation of NSCs remains unclear. METHODS In the present study, pregnant rats were exposed to 3% sevoflurane once for 2 h on gestational day 14 (G14) or 3 times for 2 h on G13, G14, and G15. Next, the differentiation of NSCs was measured using neuron marker β-tubulin III and astrocyte marker glial fibrillary acidic protein (GFAP) in fetal brain tissues 24 h and 72 h after anesthesia and in hippocampus on postnatal day 28. Primary cultured rat NSCs were exposed to 4.1% sevoflurane to explore the mechanism. RESULTS The results showed that during mid-trimester, multiple exposures to sevoflurane can cause premature differentiation of NSCs in developing brains of offspring and lead to long-term neuron reduction and astrocyte proliferation in hippocampus. The data from the present study indicated that repeated exposure to sevoflurane downregulated atrophin-1 (ATN1) expression and caused early differentiation of NSCs. Overexpression of ATN1 via lentivirus transfection attenuated the influence of sevoflurane. Using dual luciferase assay, ATN1 was found to be a target gene of microRNA-410-3p (miR-410-3p). MiR-410-3p suppression via lentivirus transfection recovered the ATN1 expression and differentiation of NSCs. CONCLUSIONS The results from the present study demonstrated that repeated exposure to sevoflurane leads to early differentiation of NSCs and long-term effects via the miR-410-3p/ATN1 pathway.
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Affiliation(s)
- Yi Zhang
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ziyi Wu
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xingyue Li
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yuxiao Wan
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yinong Zhang
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ping Zhao
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
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Yang B, Xu Z, He Z, Li X, Wu Z, Xu J, Li Q. High expression of miR-374a-5p inhibits the proliferation and promotes differentiation of Rencell VM cells by targeting Hes1. Neurosci Res 2020; 170:99-105. [PMID: 32949667 DOI: 10.1016/j.neures.2020.09.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 09/08/2020] [Accepted: 09/08/2020] [Indexed: 12/20/2022]
Abstract
The proliferation and differentiation of NSCs are regulated by miRNAs. This study investigated the role of miR-374a-5p in the proliferation and differentiation of ReNcell VM cells. ReNcell VM cells were transfected with miR-374a-5p mimic, miR-374a-5p inhibitor and Hes1, respectively. Cell proliferation was detected by clone formation assay. Target gene for miR-374a-5p was predicted by TargetScan and confirmed by dual-luciferase reporter. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the expressions of relative genes. After culturing the cells in differentiation medium, the ReNcell VM cells differentiated into βIII-tubulin (Tuj1)-positive neurons and GFAP-positive astrocytes. The miR-374a-5p expression was increased as the cells continued to differentiate. Hes1, which was predicted to be the target gene for miR-374a-5p, was low-expressed during cell differentiation. The miR-374a-5p mimic decreased cell clones, inhibited the expressions of ki-67 and Nestin, but increased those of Tuj1 and GFAP. However, miR-374a-5p inhibitor produced the opposite effects to miR-374a-5p mimic. Hes1 increased the expressions of ki-67 and Nestin, but decreased those of Tuj1 and GFAP, moreover, Hes1 reversed the role of miR-374a-5p mimic. MiR-374a-5p inhibited the proliferation of Rencell VM cells and promoted the differentiation of NSCs by reducing the Hes1 expression.
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Affiliation(s)
- Biqing Yang
- Department of Stroke Center, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Zunbao Xu
- Department of Stroke Center, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Zhiyu He
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xia Li
- Department of Neurology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Zhengdong Wu
- Department of Stroke Center, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Jiewen Xu
- Department of Stroke Center, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Qiaowei Li
- Department of Stroke Center, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China.
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Yang L, Wang H, Lü H, Hui N. Phytic acid functionalized antifouling conducting polymer hydrogel for electrochemical detection of microRNA. Anal Chim Acta 2020; 1124:104-112. [DOI: 10.1016/j.aca.2020.05.025] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 05/05/2020] [Accepted: 05/10/2020] [Indexed: 12/22/2022]
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Improta-Caria AC, Nonaka CKV, Cavalcante BRR, De Sousa RAL, Aras Júnior R, Souza BSDF. Modulation of MicroRNAs as a Potential Molecular Mechanism Involved in the Beneficial Actions of Physical Exercise in Alzheimer Disease. Int J Mol Sci 2020; 21:E4977. [PMID: 32674523 PMCID: PMC7403962 DOI: 10.3390/ijms21144977] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 06/23/2020] [Accepted: 06/23/2020] [Indexed: 12/18/2022] Open
Abstract
Alzheimer disease (AD) is one of the most common neurodegenerative diseases, affecting middle-aged and elderly individuals worldwide. AD pathophysiology involves the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain, along with chronic neuroinflammation and neurodegeneration. Physical exercise (PE) is a beneficial non-pharmacological strategy and has been described as an ally to combat cognitive decline in individuals with AD. However, the molecular mechanisms that govern the beneficial adaptations induced by PE in AD are not fully elucidated. MicroRNAs are small non-coding RNAs involved in the post-transcriptional regulation of gene expression, inhibiting or degrading their target mRNAs. MicroRNAs are involved in physiological processes that govern normal brain function and deregulated microRNA profiles are associated with the development and progression of AD. It is also known that PE changes microRNA expression profile in the circulation and in target tissues and organs. Thus, this review aimed to identify the role of deregulated microRNAs in the pathophysiology of AD and explore the possible role of the modulation of microRNAs as a molecular mechanism involved in the beneficial actions of PE in AD.
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Affiliation(s)
- Alex Cleber Improta-Caria
- Post-Graduate Program in Medicine and Health, Faculty of Medicine, Federal University of Bahia, Bahia 40110-909, Brazil; (A.C.I.-C.); (R.A.J.)
- University Hospital Professor Edgard Santos, Bahia 40110-909, Brazil
- Center for Biotechnology and Cell Therapy, São Rafael Hospital, Bahia 40110-909, Brazil; (C.K.V.N.); (B.R.R.C.)
| | - Carolina Kymie Vasques Nonaka
- Center for Biotechnology and Cell Therapy, São Rafael Hospital, Bahia 40110-909, Brazil; (C.K.V.N.); (B.R.R.C.)
- D’Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil
| | - Bruno Raphael Ribeiro Cavalcante
- Center for Biotechnology and Cell Therapy, São Rafael Hospital, Bahia 40110-909, Brazil; (C.K.V.N.); (B.R.R.C.)
- D’Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Bahia 40110-909, Brazil
| | - Ricardo Augusto Leoni De Sousa
- Physiological Science Multicentric Program, Federal University of Valleys´ Jequitinhonha and Mucuri, Minas Gerais 30000-000, Brazil;
| | - Roque Aras Júnior
- Post-Graduate Program in Medicine and Health, Faculty of Medicine, Federal University of Bahia, Bahia 40110-909, Brazil; (A.C.I.-C.); (R.A.J.)
- University Hospital Professor Edgard Santos, Bahia 40110-909, Brazil
| | - Bruno Solano de Freitas Souza
- Center for Biotechnology and Cell Therapy, São Rafael Hospital, Bahia 40110-909, Brazil; (C.K.V.N.); (B.R.R.C.)
- D’Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Bahia 40110-909, Brazil
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Kempfle JS, Luu NNC, Petrillo M, Al-Asad R, Zhang A, Edge ASB. Lin28 reprograms inner ear glia to a neuronal fate. Stem Cells 2020; 38:890-903. [PMID: 32246510 PMCID: PMC10908373 DOI: 10.1002/stem.3181] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 02/05/2020] [Accepted: 02/08/2020] [Indexed: 12/16/2022]
Abstract
Sensorineural hearing loss is irreversible and can be caused by loss of auditory neurons. Regeneration of neural cells from endogenous cells may offer a future tool to restore the auditory circuit and to enhance the performance of implantable hearing devices. Neurons and glial cells in the peripheral nervous system are closely related and originate from a common progenitor. Prior work in our lab indicated that in the early postnatal mouse inner ear, proteolipid protein 1 (Plp1) expressing glial cells could act as progenitor cells for neurons in vitro. Here, we used a transgenic mouse model to transiently overexpress Lin28, a neural stem cell regulator, in Plp1-positive glial cells. Lin28 promoted proliferation and conversion of auditory glial cells into neurons in vitro. To study the effects of Lin28 on endogenous glial cells after loss of auditory neurons in vivo, we produced a model of auditory neuropathy by selectively damaging auditory neurons with ouabain. After neural damage was confirmed by the auditory brainstem response, we briefly upregulated the Lin28 in Plp1-expressing inner ear glial cells. One month later, we analyzed the cochlea for neural marker expression by quantitative RT-PCR and immunohistochemistry. We found that transient Lin28 overexpression in Plp1-expressing glial cells induced expression of neural stem cell markers and subsequent conversion into neurons. This suggests the potential for inner ear glia to be converted into neurons as a regeneration therapy for neural replacement in auditory neuropathy.
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Affiliation(s)
- Judith S. Kempfle
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts
- Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts
- University Department of Otolaryngology, Head and Neck Surgery, Tübingen, Germany
| | - Ngoc-Nhi C. Luu
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts
- Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts
- University Department of Otolaryngology, Head and Neck Surgery, Zürich, Switzerland
| | - Marco Petrillo
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts
- Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Reef Al-Asad
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts
- Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Andrea Zhang
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts
- Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Albert S. B. Edge
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts
- Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts
- Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, Massachusetts
- Harvard Stem Cell Institute, Cambridge, Massachusetts
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Gao H, Ni N, Zhang D, Wang Y, Tang Z, Sun N, Ju Y, Dai X, Zhang Y, Liu Y, Gu P. miR-762 regulates the proliferation and differentiation of retinal progenitor cells by targeting NPDC1. Cell Cycle 2020; 19:1754-1767. [PMID: 32544377 DOI: 10.1080/15384101.2020.1777805] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Retinal degenerations, which lead to irreversible decline in visual function, are still no effective recovery treatments. Currently, retinal progenitor cell (RPC) transplantation therapy is expected to provide a new approach to treat these diseases; however, the limited proliferation capacity and differentiation potential toward specific retinal neurons of RPCs hinder their potential clinical applications. microRNAs have been reported to serve as important regulators in the cell fate determination of stem/progenitor cells. In this study, our data demonstrated that miR-762 inhibited NPDC1 expression to positively regulate RPC proliferation and suppress RPC neuronal differentiation. Furthermore, the knockdown of miR-762 upregulated NPDC1 expression in RPCs, leading to the inhibition of RPC proliferation and the increase in neuronal differentiation. Moreover, NPDC1 could rescue anti-miR-762-induced RPC proliferation deficiency and the inhibitory effect of miR-762 on RPC differentiation. In conclusion, our study demonstrated that miR-762 plays a crucial role in regulating RPC proliferation and differentiation by directly targeting NPDC1, which is firstly reported that microRNAs positively regulate RPC proliferation and negatively regulate RPC differentiation, which provides a comprehensive understanding of the molecular mechanisms that dominate RPC proliferation and differentiation in vitro.
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Affiliation(s)
- Huiqin Gao
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Ni Ni
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Dandan Zhang
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Yuyao Wang
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Zhimin Tang
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Na Sun
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Yahan Ju
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Xiaochan Dai
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Yidan Zhang
- Department of Ophthalmology, Shanghai Children's Hospital, Shanghai Jiao Tong University , Shanghai, P.R. China
| | - Yan Liu
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
| | - Ping Gu
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, P.R. China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, P.R. China
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Xue C, Kang B, Su P, Wang D, Zhao F, Zhang J, Wang X, Lang H, Cao Z. MicroRNA-106b-5p participates in lead (Pb 2+)-induced cell viability inhibition by targeting XIAP in HT-22 and PC12 cells. Toxicol In Vitro 2020; 66:104876. [PMID: 32344020 DOI: 10.1016/j.tiv.2020.104876] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 04/20/2020] [Accepted: 04/23/2020] [Indexed: 12/25/2022]
Abstract
Previous studies reported perturbed expressing of X-linked inhibitor of apoptosis protein (XIAP) under lead (Pb) exposure. However, researches on XIAP expression mainly focused on its transcriptional and post-translational regulation, rarely involving post-transcriptional mechanism manipulated by certain indispensable microRNAs (miRNAs). Interestingly, we unveiled that miR-106b-5p, a widely expressed miRNA in various tissues, is up-regulated by Pb2+-induced stress. Moreover, we found a binding site for miR-106b-5p in the 3'-UTR of xiap mRNA using bioinformatics analysis, and provided the evidences that miR-106b-5p can interact and function with this regulatory region via luciferase reporter assay. Our results further showed that miR-106b-5p down-regulates XIAP protein level, and suppression of miR-106b-5p reverses the decrease in both XIAP level and cell viability in Pb2+-treated HT-22 and PC12 cells. In brief, we identified a novel function of miR-106b-5p in the post-transcriptional regulation of XIAP expression associated with Pb neurotoxicity.
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Affiliation(s)
- Chong Xue
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China
| | - Beipei Kang
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China; Department of Clinical Laboratory, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, China
| | - Peng Su
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China
| | - Diya Wang
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China
| | - Fang Zhao
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China
| | - Jianbin Zhang
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China
| | - Xiaojing Wang
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China; Department of Neurology and Endocrinology, 989 Hospital of PLA, Pingdingshan 467021, China
| | - Haiyang Lang
- School of Public Health, Air Force Military Medical University, Xi'an 710032, China.
| | - Zipeng Cao
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Military Medical University, Xi'an 710032, China.
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Rajabi H, Aslani S, Abhari A, Sanajou D. Expression Profiles of MicroRNAs in Stem Cells Differentiation. Curr Pharm Biotechnol 2020; 21:906-918. [PMID: 32072899 DOI: 10.2174/1389201021666200219092520] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 12/06/2019] [Accepted: 02/06/2020] [Indexed: 12/12/2022]
Abstract
Stem cells are undifferentiated cells and have a great potential in multilineage differentiation. These cells are classified into adult stem cells like Mesenchymal Stem Cells (MSCs) and Embryonic Stem Cells (ESCs). Stem cells also have potential therapeutic utility due to their pluripotency, self-renewal, and differentiation ability. These properties make them a suitable choice for regenerative medicine. Stem cells differentiation toward functional cells is governed by different signaling pathways and transcription factors. Recent studies have demonstrated the key role of microRNAs in the pathogenesis of various diseases, cell cycle regulation, apoptosis, aging, cell fate decisions. Several types of stem cells have different and unique miRNA expression profiles. Our review summarizes novel regulatory roles of miRNAs in the process of stem cell differentiation especially adult stem cells into a variety of functional cells through signaling pathways and transcription factors modulation. Understanding the mechanistic roles of miRNAs might be helpful in elaborating clinical therapies using stem cells and developing novel biomarkers for the early and effective diagnosis of pathologic conditions.
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Affiliation(s)
- Hadi Rajabi
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Somayeh Aslani
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Abhari
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Davoud Sanajou
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Liu Y, Yu M, Jiang D. Downregulation of STAT1 induces the differentiation of neural stem cells through JNK pathway. Tissue Cell 2019; 61:61-66. [PMID: 31759408 DOI: 10.1016/j.tice.2019.09.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 09/10/2019] [Accepted: 09/13/2019] [Indexed: 01/13/2023]
Abstract
Neural stem cells (NSCs) generated neurons and glial cells. Thus, it is a preferable candidate to the cell replacement-based therapy against neural disorders. The signaling pathways that regulate differentiation of NSCs are widely studied. In the current study, we used in vitro culture system to elucidate the role of signal transducer and activator of transcription 1 (STAT1) in NSCs' differentiation. Downregulation of STAT1 inhibited the proliferation of NSCs. Meanwhile, we also found STAT1 regulation could control the differentiation of NSCs. More neurons and glia cells were generated from NSCs with STAT1 silencing. This process was mediated by the JNK/STAT1 signaling. STAT1 inhibitor promoted differentiation of NSCs. After transplantation, we observed more neurons generated from NSCs with shRNA-STAT1 treatment. Collectively, this work showed an efficient way to regulate neuronal differentiation of NSCs through regulating the STAT1 expression. This is likely to provide source and theoretical support to cell replacement based theory.
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Affiliation(s)
- Yigang Liu
- Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China
| | - Min Yu
- Department of Neurology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
| | - Dudu Jiang
- Department of Neurology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China.
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Ding Y, Wang R, Wang X, Cong P, Liu Y, Li Z, Xu J, Xue C. Preparation and effects on neuronal nutrition of plasmenylethonoamine and plasmanylcholine from the mussel Mytilus edulis. Biosci Biotechnol Biochem 2019; 84:380-392. [PMID: 31608790 DOI: 10.1080/09168451.2019.1674632] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Plasmenylethonoamine (pPE) and plasmanylcholine (aPC) are important phospholipid subclasses. Herein we explored optimum conditions for enzymatic purification and preparation of pPE and aPC from the mussel Mytilus edulis and bovine brain. Among them, pPE in Mytilus edulis PE was mainly p18:0-20:5 and p18:0-22:6, and its purity was 92.7%; aPC in PC was primarily a16:0-22:6 and a16:0-20:5, and aPC accounted for 90.2% of PC. We thereafter evaluated neurotrophic effects of Mytilus edulis pPE, aPC, and bovine brain pPE in a NGF-induced PC12 cell model. Morphologically, pPE and aPC could both promote differentiation, manifested in a significant increase in neurite length and number, due to increased expression of synaptophysin and growth protein GAP-43 in a dose-independent and structure-selective manner. Importantly, the effect on neuronal nutrition of pPE was better than aPC, and marine pPE was better than terrestrial pPE, which might be ascribed to vinyl-ether bond and differences in fatty acid composition.Abbreviations: AA: arachidonic acid; DHA: docosahexaenoic acid; EIC: extracted ion chromatogram; EPA: eicosapentanoic acid; GAP: growth-associated protein; HPLC: high-performance liquid chromatography; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LPC: lyso-PC; LPE: lyso-PE; MS: mass spectrometry; NGF: nerve growth factor; PC: phosphatidylcholine; aPC: plasmanylcholine; PE: phosphatidylethanolamine; pPE: plasmenylethonoamine; PG: phosphoglycerols; PLs: phospholipids; PS: phosphoserines; TIC: total ion chromatogram.
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Affiliation(s)
- Yi Ding
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China
| | - Rui Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China
| | - Xiaoxu Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China
| | - Peixu Cong
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China
| | - Yanjun Liu
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China
| | - Zhaojie Li
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China
| | - Jie Xu
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China.,Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, Shandong Province, China
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48
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Chen J, Chen T, Zhu Y, Li Y, Zhang Y, Wang Y, Li X, Xie X, Wang J, Huang M, Sun X, Ke Y. circPTN sponges miR-145-5p/miR-330-5p to promote proliferation and stemness in glioma. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2019; 38:398. [PMID: 31511040 PMCID: PMC6737709 DOI: 10.1186/s13046-019-1376-8] [Citation(s) in RCA: 175] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 08/11/2019] [Indexed: 01/06/2023]
Abstract
Background Growing evidences indicate that circular RNAs (circRNAs) play an important role in the regulation of biological behavior of tumor. We aim to explore the role of circRNA in glioma and elucidate how circRNA acts. Methods Real-time PCR was used to examine the expression of circPTN in glioma tissues and normal brain tissues (NBT). Assays of dual- luciferase reporter system, biotin label RNA pull-down and FISH were used to determine that circPTN could sponge miR-145-5p and miR-330-5p. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell (GSCs). Cell counting Kit-8 (CCK8), EdU assay and flow cytometry were used to investigate proliferation and cell cycle. Intracranial xenograft was established to determine how circPTN impacts in vivo. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell (GSCs). Results We demonstrated circPTN was significantly higher expression in glioma tissues and glioma cell lines, compared with NBT and HEB (human astrocyte). In gain- and loss-of-function experiments, circPTN significantly promoted glioma growth in vitro and in vivo. Furthermore, we performed dual-luciferase reporter assays and RNA pull-down assays to verify that circPTN acts through sponging miR-145-5p and miR-330-5p. Increasing expression of circPTN rescued the inhibition of proliferation and downregulation of SOX9/ITGA5 in glioma cells by miR-145-5p/miR-330-5p. In addition, we found that circPTN promoted self-renewal and increased the expression of stemness markers (Nestin, CD133, SOX9, and SOX2) via sponging miR-145-5p. Moreover, this regulation was disappeared when circPTN binding sites in miR-145-5p were mutated. Conclusions Our results suggest that circPTN is an oncogenic factor that acts by sponging miR-145-5p/miR-330-5p in glioma. Electronic supplementary material The online version of this article (10.1186/s13046-019-1376-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jiansheng Chen
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China.,Department of Neurosurgery, Huizhou Municipal Central Hospital, Huizhou Shi, China
| | - Taoliang Chen
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Yubo Zhu
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Yan Li
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Yuxuan Zhang
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Yun Wang
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Xiao Li
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Xiaomi Xie
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Jihui Wang
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Min Huang
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China.
| | - Xinlin Sun
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China
| | - Yiquan Ke
- The National Key Clinical Specialty; Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Industrial Road No.253, Guangzhou, 510282, Guangdong, China.
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Qian C, Wang B, Zou Y, Zhang Y, Hu X, Sun W, Xiao H, Liu H, Shi L. MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin. Cancer Manag Res 2019; 11:6829-6840. [PMID: 31440081 PMCID: PMC6664422 DOI: 10.2147/cmar.s210076] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 05/30/2019] [Indexed: 12/13/2022] Open
Abstract
Background: The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis. Purpose: The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC. Patients and methods: qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot. Results: miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment. Conclusion: Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.
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Affiliation(s)
- Chunfa Qian
- Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China
| | - Bin Wang
- Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, People's Republic of China
| | - Yuanjie Zou
- Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China
| | - Yansong Zhang
- Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China
| | - Xinhua Hu
- Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China
| | - Wenbo Sun
- Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China
| | - Hong Xiao
- Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China
| | - Hongyi Liu
- Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China
| | - Lei Shi
- Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, People's Republic of China
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50
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Xu C, Wang C, Meng Q, Gu Y, Wang Q, Xu W, Han Y, Qin Y, Li J, Jia S, Xu J, Zhou Y. miR‑153 promotes neural differentiation in the mouse hippocampal HT‑22 cell line and increases the expression of neuron‑specific enolase. Mol Med Rep 2019; 20:1725-1735. [PMID: 31257504 PMCID: PMC6625396 DOI: 10.3892/mmr.2019.10421] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 05/06/2019] [Indexed: 01/22/2023] Open
Abstract
MicroRNAs (miRNAs) have been found to play important regulatory roles in certain neurodegenerative diseases. The aim of the present study was to investigate the effect of miRNA-153 (miR-153) on the neural differentiation of HT-22 cells. Overexpression of miR-153 induced the differentiation of HT-22 cells, increasing the number of protrusions and branches, reducing the S phase distribution of the cell cycle, and attenuating the cell proliferation rate as determined using the Cell Counting Kit-8 assay. Furthermore, miR-153 increased the expression of neuron-specific γ-enolase (NSE), neuronal nuclei (NeuN), and N-ethylmaleimide-sensitive fusion attachment protein 23 (SNAP23) and SNAP25 at the transcriptional and protein level by PCR and western blot analysis. Moreover, miR-153 caused obvious upregulation of peroxiredoxin 5 (PRX5), which has been found to protect neural cells from death and apoptosis. miR-153 promoted neural differentiation and protected neural cells by upregulating the neuron markers γ-enolase, neuronal nuclei, and the functional proteins SNAP23, SNAP25 and PRX5. Therefore, miR-153 may be a potential target for the treatment of certain neurodegenerative diseases.
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Affiliation(s)
- Chunli Xu
- Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Chen Wang
- School of Life Science and Technology, School of Medicine, Tongji University, Shanghai 200092, P.R. China
| | - Qiuyu Meng
- School of Life Science and Technology, School of Medicine, Tongji University, Shanghai 200092, P.R. China
| | - Yuming Gu
- Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Qiwei Wang
- Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Wenjie Xu
- Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Ying Han
- Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Yong Qin
- Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Jiao Li
- Teaching Laboratory Center of Medicine and Life Science, School of Medicine, Tongji University, Shanghai 200092, P.R. China
| | - Song Jia
- Teaching Laboratory Center of Medicine and Life Science, School of Medicine, Tongji University, Shanghai 200092, P.R. China
| | - Jie Xu
- Teaching Laboratory Center of Medicine and Life Science, School of Medicine, Tongji University, Shanghai 200092, P.R. China
| | - Yixin Zhou
- Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
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