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1
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Kaur V, Sunkaria A. Unlocking the therapeutic promise of miRNAs in promoting amyloid-β clearance for Alzheimer's disease. Behav Brain Res 2025; 484:115505. [PMID: 40010509 DOI: 10.1016/j.bbr.2025.115505] [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: 10/22/2024] [Revised: 01/06/2025] [Accepted: 02/21/2025] [Indexed: 02/28/2025]
Abstract
Alzheimer's disease (AD) is a neurological disorder that affects cognition and behavior, accounting for 60-70 % of dementia cases. Its mechanisms involve amyloid aggregates, hyperphosphorylated tau tangles, and loss of neural connections. Current treatments have limited efficacy due to a lack of specific targets. Recently, microRNAs (miRNAs) have emerged as key modulators in AD, regulating gene expression through interactions with mRNA. Dysregulation of specific miRNAs contributes to disease progression by disrupting clearance pathways. Antisense oligonucleotide (ASO)-based therapies show promise for AD treatment, particularly when combined with miRNA mimics or antagonists, targeting complex regulatory networks. However, miRNAs can interact with each other, complicating cellular processes and potentially leading to side effects. Our review emphasizes the role of miRNAs in regulating amyloid-beta (Aβ) clearance and highlights their potential as therapeutic targets and early biomarkers for AD, underscoring the need for further research to enhance their efficacy and safety.
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Affiliation(s)
- Vajinder Kaur
- Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab 143005, India
| | - Aditya Sunkaria
- Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
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2
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Mallis P. Hypoxic endometrial epithelial cell-derived microRNAs effectively regulate the regenerative properties of mesenchymal stromal cells. World J Stem Cells 2025; 17:102482. [PMID: 40308881 PMCID: PMC12038455 DOI: 10.4252/wjsc.v17.i4.102482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 02/06/2025] [Accepted: 03/05/2025] [Indexed: 04/23/2025] Open
Abstract
Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement. However, a thin endometrial layer (≤ 7 mm) may have a significant effect on microenvironment tolerance, which is further related to successful embryo implantation or conception, either naturally or after assisted reproductive technology. Moreover, this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells (EECs), which results in altered signaling biomolecule secretion, including exosome content. In the context of endometrium regeneration, mesenchymal stromal cells (MSCs) and umbilical cord (UC)-derived stem cells have been applied in clinical trials with promising results. It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs. Specifically, microRNAs in exosomes secreted by the hypoxic damaged EECs, such as miR-214-5p and miR-21-5p, play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Taking into consideration the above information, UC-MSCs may be considered as a modern intervention for endometrial regeneration.
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Affiliation(s)
- Panagiotis Mallis
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, Athens 11527, Attikí, Greece.
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AbdElneam AI, Al-Dhubaibi MS, Bahaj SS, Mohammed GF, Atef LM. Assessment of miR-19b-3p, miR-182-5p, and miR-155-5p expression and its relation. Arch Dermatol Res 2025; 317:619. [PMID: 40119951 DOI: 10.1007/s00403-025-04043-y] [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: 11/03/2024] [Revised: 02/07/2025] [Accepted: 02/12/2025] [Indexed: 03/25/2025]
Abstract
Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss. Despite the growing understanding of its immune-related pathogenesis, biomarkers for early diagnosis and disease severity assessment remain limited. Recent studies have suggested that microRNAs (miRNAs) play a crucial role in regulating immune responses and inflammation in autoimmune diseases. This study aimed to investigate the expression levels of three miRNAs, miR-19b-3p, miR-182-5p, and miR-155-5p, in AA patients and their potential as diagnostic markers and indicators of disease severity. A total of 67 AA patients and 62 healthy controls were included in this case-control study. The severity of AA was evaluated using the Severity of Alopecia Tool (SALT) score, categorizing patients into mild, moderate, and severe groups. Plasma miRNA extraction was performed using the Direct-zol™ RNA MiniPrep kit, and qRT-PCR analysis was conducted to quantify the expression levels of miR-19b-3p, miR-182-5p, and miR-155-5p. Diagnostic accuracy was assessed using Receiver Operating Characteristic (ROC) curve analysis, and correlation analysis was performed to examine the relationship between miRNA expression and disease severity. The results revealed that the expression of miR-19b-3p, miR-182-5p, and miR-155-5p was significantly higher in AA patients compared to healthy controls (p = 0.001 for all three miRNAs). ROC curve analysis demonstrated high diagnostic accuracy, with AUC values of 0.99 for miR-19b-3p, 0.95 for miR-182-5p, and 0.97 for miR-155-5p. These miRNAs showed high sensitivity and specificity, indicating their strong potential as diagnostic biomarkers. Moreover, correlation analysis revealed a significant association between miR-155-5p expression and the severity of AA (p < 0.001), suggesting its potential as a marker of disease progression. This study highlights the significant upregulation of miR-19b-3p, miR-182-5p, and miR-155-5p in AA patients, indicating their potential as minimally invasive diagnostic markers. Furthermore, the correlation between miRNA expression and disease severity provides valuable insights into the molecular mechanisms underlying AA. These findings suggest that miRNAs, particularly miR-155-5p, may serve as promising biomarkers for diagnosing and monitoring the progression of AA, potentially aiding in the development of targeted therapeutic strategies.
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Affiliation(s)
- Ahmed Ibrahim AbdElneam
- Department of Clinical Biochemistry, Department of Basic Medical Sciences, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia
- Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute, National Research Center, 33 El Bohouth St. (Former El Tahrir St.), Dokki 12622, Cairo, Egypt
| | | | - Saleh Salem Bahaj
- Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen
| | - Ghada Farouk Mohammed
- Department of Dermatology, Venereology, and Sexology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
| | - Lina Mohammed Atef
- Department of Dermatology, Venereology, and Sexology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
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Schüle S, Hackenbroch C, Beer M, Ostheim P, Hermann C, Muhtadi R, Stewart S, Port M, Scherthan H, Abend M. Tin prefiltration in computed tomography does not significantly alter radiation-induced gene expression and DNA double-strand break formation. PLoS One 2024; 19:e0315808. [PMID: 39705301 DOI: 10.1371/journal.pone.0315808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 12/02/2024] [Indexed: 12/22/2024] Open
Abstract
BACKGROUND The tin (Sn) prefilter technique is a recently introduced dose-saving technique in computed tomography (CT). This study investigates whether there is an altered molecular biological response in blood cells using the tin prefiltering technique. METHODS Blood from 6 donors was X-irradiated ex-vivo with 20 mGy full dose (FD) protocols (Sn 150 kV, 150 kV, and 120 kV) and a tin prefiltered 16.5 mGy low dose (LD) protocol on a CT scanner. Biological changes were determined by quantification of γH2AX DNA double-strand break (DSB) foci, and differential gene expression (DGE) relative to unexposed samples were examined for seven known radiation-induced genes (FDXR, DDB2, BAX, CDKN1A, AEN, EDA2R, APOBEC3H) and 667 microRNAs (miRNA). RESULTS EDA2R and DDB2 gene expression (GE) increased 1.7-6-fold (p = 0.0004-0.02) and average DNA DSB foci value (0.31±0.02, p<0.0001) increased significantly relative to unexposed samples, but similarly for the applied radiation protocols. FDXR upregulation (2.2-fold) was significant for FD protocols (p = 0.01-0.02) relative to unexposed samples. miRNA GE changes were not significant (p = 0.15-1.00) and DGE were similar for the examined protocols (p = 0.10-1.00). An increased frequency of lower DGE values was seen in the Sn 150 kV LD protocol compared to the 120 kV FD and Sn 150 kV FD protocols (p = 0.001-0.008). CONCLUSIONS The current ex-vivo study indicates no changes regarding transcriptional and post-transcriptional DGE and DNA DSB induction when using the tin prefilter technique and even a significant tendency to lower radiation-induced DGE-changes due to the dose reduction of the tin prefilter with equal image quality compared to classical CT scan protocols was found.
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Affiliation(s)
- Simone Schüle
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
- Department of Diagnostic and Interventional Radiology and Neuroradiology, German Armed Forces Hospital of Ulm, Ulm, Baden-Württemberg, Germany
- Department of Radiology, University Hospital of Ulm, Ulm, Baden-Württemberg, Germany
| | - Carsten Hackenbroch
- Department of Diagnostic and Interventional Radiology and Neuroradiology, German Armed Forces Hospital of Ulm, Ulm, Baden-Württemberg, Germany
- Department of Radiology, University Hospital of Ulm, Ulm, Baden-Württemberg, Germany
| | - Meinrad Beer
- Department of Radiology, University Hospital of Ulm, Ulm, Baden-Württemberg, Germany
| | - Patrick Ostheim
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
- Department of Radiology, University Hospital Regensburg, Regensburg, Bavaria, Germany
| | - Cornelius Hermann
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
| | - Razan Muhtadi
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
| | - Samantha Stewart
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
| | - Matthias Port
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
| | - Harry Scherthan
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
| | - Michael Abend
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich, Bavaria, Germany
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Purewal JS, Doshi GM. RNAi in psoriasis: A melodic exploration of miRNA, shRNA, and amiRNA with a spotlight on siRNA. Eur J Pharmacol 2024; 985:177083. [PMID: 39481628 DOI: 10.1016/j.ejphar.2024.177083] [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: 06/25/2024] [Revised: 10/28/2024] [Accepted: 10/29/2024] [Indexed: 11/02/2024]
Abstract
Psoriasis (Pso) is an autoimmune inflammatory skin disease characterised by well-demarcated, red plaques covered in silver scales. It affects people of all ages and can be passed down through generations. Genetics play an important role in determining vulnerability to develop Pso. Several large-scale genome-wide association studies have identified over 80 genetic loci associated with Pso susceptibility. Gene expression can be regulated via RNA interference (RNAi). RNAi suppresses gene expression by degrading mRNA molecules. Since its discovery, RNAi has generated considerable excitement over its potential therapeutic benefits. RNAi is mediated by endogenous small RNA molecules like microRNA (miRNA) or exogenous small RNA molecules like small interfering RNA (siRNA), short hairpin RNA (shRNA), and artificial micro RNA (amiRNA). These small RNA molecules can silence a disease-related gene in a sequence-specific manner. Targeting RNAi pathways can help modify disease-related biological processes in various medical conditions, including autoimmune disorders. In Pso, RNAi can downregulate the expression of molecules involved in the pathophysiology of the disease. Significant progress has been made in the field of RNAi therapeutics. However, further research is needed to fine-tune the design and delivery of RNAi therapeutics in humans. In this review, we discuss various effectors of RNAi, some challenges related to RNAi therapeutics (emphasizing siRNA) and strategies to overcome these challenges. Furthermore, we have discussed some studies that employ RNAi therapeutics for Pso.
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Aggeletopoulou I, Tsounis EP, Triantos C. Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights. Int J Mol Sci 2024; 25:4901. [PMID: 38732118 PMCID: PMC11084591 DOI: 10.3390/ijms25094901] [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: 03/15/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition characterized by abnormal fat accumulation in the liver, often associated with metabolic disorders. Emerging evidence suggests a potential link between vitamin D deficiency and the development and progression of MASLD. The current review provides a concise overview of recent studies uncovering novel mechanistic insights into the interplay between vitamin D and MASLD. Several epidemiological studies have highlighted a significant association between low vitamin D levels and an increased risk of MASLD. Vitamin D, traditionally known for its role in bone health, has now been recognized as a key player in various physiological processes, including immune regulation and inflammation. Experimental studies using animal models have demonstrated that vitamin D deficiency exacerbates liver steatosis and inflammation, suggesting a potential protective role against MASLD. Mechanistically, vitamin D appears to modulate MASLD through multiple pathways. Firstly, the vitamin D receptor (VDR) is abundantly expressed in liver cells, indicating a direct regulatory role in hepatic function. Activation of the VDR has been shown to suppress hepatic lipid accumulation and inflammation, providing a mechanistic basis for the observed protective effects. Additionally, vitamin D influences insulin sensitivity, a critical factor in MASLD pathogenesis. Improved insulin sensitivity may mitigate the excessive accumulation of fat in the liver, thus attenuating MASLD progression. In parallel, vitamin D exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines implicated in MASLD pathophysiology. Experimental evidence suggests that the immunomodulatory effects of vitamin D extend to the liver, reducing inflammation and oxidative stress, key drivers of MASLD, and the likelihood of hepatocyte injury and fibrosis. Understanding the complex interplay between vitamin D and MASLD provides a basis for exploring targeted therapeutic strategies and preventive interventions. As vitamin D deficiency is a modifiable risk factor, addressing this nutritional concern may prove beneficial in mitigating the burden of MASLD and associated metabolic disorders.
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Affiliation(s)
| | | | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
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Singh S, Saxena S, Sharma H, Paudel KR, Chakraborty A, MacLoughlin R, Oliver BG, Gupta G, Negi P, Singh SK, Dua K. Emerging role of tumor suppressing microRNAs as therapeutics in managing non-small cell lung cancer. Pathol Res Pract 2024; 256:155222. [PMID: 38452582 DOI: 10.1016/j.prp.2024.155222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 02/12/2024] [Accepted: 02/21/2024] [Indexed: 03/09/2024]
Abstract
Lung cancer (LC) is the second leading cause of death across the globe after breast cancer. There are two types of LC viz. small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all LC cases. NSCLC affects smokers and people who do not smoke and mainly arises in bronchi and peripheral lungs tissue. LC is often characterized by the alterations of key genes such as EGFR, Wnt/β-catenin signaling, ALK, MET, K-Ras and p53 and downstream signaling pathways associated with tumor growth, differentiation, and survival. Numerous miRNAs have been discovered as a result of advances in biotechnology to treat LC. Various miRNAs those have been identified to treat LC include mir-Let7, mir-34a, mir-134, mir-16-1, mir-320a, mir-148a, mir-125a-5p, mir-497, mir-29, mir-133a, and mir-29a-3p. These miRNAs target various signaling pathways that are involved in pathogenesis of LC. However, due to rapid RNAse degradation, quick clearance, and heat instability, associated with necked miRNA leads to less effective therapeutic effect against LC. Therefore, to overcome these challenges nanocarrier loaded with miRNAs have been reported. They have been found promising because they have the capacity to target the tumor as well as they can penetrate the tumors deep due to nanometer size. Some of the clinical trials have been performed using miR-34a and let-7 for the treatment of LC. In the present manuscript we highlight the role miRNAs as well as their nanoparticle in tumor suppression.
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Affiliation(s)
- Shubham Singh
- Department of Biotechnology, School of Bioengineering and Biosciences, Faculty of Technology and Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
| | - Sangeeta Saxena
- Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
| | - Himani Sharma
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Keshav Raj Paudel
- Centre for Inflammation, Centenary Institute and the University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, New South Wales, Australia
| | - Amlan Chakraborty
- Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PL, UK; Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia
| | - Ronan MacLoughlin
- Aerogen, IDA Business Park, Dangan, Galway H91 HE94, Ireland; School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland; School of Pharmacy & Pharmaceutical Sciences, Trinity College, Dublin D02 PN40, Ireland
| | - Brian G Oliver
- Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia; School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Gaurav Gupta
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Poonam Negi
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173212, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology, Sydney, Ultimo, NSW 2007, Australia.
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology, Sydney, Ultimo, NSW 2007, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology, Sydney, Ultimo, NSW 2007, Australia.
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Wydorski PJ, Kozlowska W, Zmijewska A, Franczak A. Exposure to the extremely low-frequency electromagnetic field induces changes in the epigenetic regulation of gene expression in the endometrium. Theriogenology 2024; 217:72-82. [PMID: 38262222 DOI: 10.1016/j.theriogenology.2024.01.015] [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: 10/18/2023] [Revised: 01/10/2024] [Accepted: 01/14/2024] [Indexed: 01/25/2024]
Abstract
Increasing technological development results in more sources of the extremely low-frequency electromagnetic field (ELF-EMF), which is recognized as an environmental risk factor. The results of the past study indicate that the ELF-EMF can affect the level of DNA methylation. The study aimed to determine whether the ELF-EMF induces changes in epigenetic regulation of gene expression in the endometrium of pigs during the peri-implantation period. Endometrial slices (100 ± 5 mg) collected on days 15-16 of pregnancy were exposed in vitro to the ELF-EMF at a frequency of 50 Hz for 2 h of treatment duration. To determine the impact of the ELF-EMF on elements of epigenetic regulations involved in DNA methylation, histone modification, and microRNA biogenesis in the endometrium, the DNMT1 and DNMT3a; EZH2, UHRF1, and MBD1; DICER1 and DGCR8 mRNA transcript and protein abundance were analyzed using Real-Time PCR and Western blot, respectively. Moreover, EED and SUZ12 mRNA transcript, global DNA methylation, and the activity of histone deacetylase (HDAC) were analyzed. The changes in the abundance of DNMT1 and DNMT3a, EZH2 mRNA transcript and protein, EED and SUZ12 mRNA transcript, global DNA methylation level, HDAC activity, and the abundance of proteins involved in microRNA biogenesis evoked by the ELF-EMF in the endometrium were observed. The ELF-EMF possesses the potential to alter epigenetic regulation of gene expression in the porcine endometrium. Observed alterations may be the reason for changes in the transcriptomic profile of the endometrium exposed to the ELF-EMF which in turn may disrupt biological processes in the uterus during peri-implantation.
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Affiliation(s)
- Pawel Jozef Wydorski
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A, 10-719, Olsztyn, Poland.
| | - Wiktoria Kozlowska
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A, 10-719, Olsztyn, Poland.
| | - Agata Zmijewska
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A, 10-719, Olsztyn, Poland.
| | - Anita Franczak
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A, 10-719, Olsztyn, Poland.
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9
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Rafiyian M, Gouyandeh F, Saati M, Davoodvandi A, Rasooli Manesh SM, Asemi R, Sharifi M, Asemi Z. Melatonin affects the expression of microRNA-21: A mini-review of current evidence. Pathol Res Pract 2024; 254:155160. [PMID: 38277748 DOI: 10.1016/j.prp.2024.155160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/18/2024] [Accepted: 01/18/2024] [Indexed: 01/28/2024]
Abstract
Melatonin (MLT) is an endogenous hormone produced by pineal gland which possess promising anti-tumor effects. Anti-inflammatory and anti-oxidant properties of MLT, along with its immunomodulatory, proapoptotic, and anti-angiogenic properties, are often referred to the main mechanisms of its anti-tumor effects. Recent evidence has suggested that epigenetic alterations are also involved in the anti-tumor properties of MLT. Among these MLT-induced epigenetic alterations is modulation of the expression of several oncogenic and tumor suppressor microRNAs(miRNAs). MiRNAs are among the most promising and potential therapeutic and diagnostic tools in different diseases and enhanced the development of better therapeutic drugs. Suppression of oncomicroRNAs such as microRNA-21, - 20a, and - 27a as well as, up-regulation of microRNA-34 a/c are among the most important effects of MLT on microRNAs homeostasis. Recently, miR-21 has attracted the attention of scientists due to the its wide range of effects on different cancers and diseases. Regulation of this RNA may be a key to the development of better therapeutic targets. The present review will summarize the findings of in vitro and experimental studies of MLT-induced impacts on the expression of microRNAs which are involved in different models and numerous stages of tumor initiation, growth, metastasis, and chemo-resistance.
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Affiliation(s)
- Mahdi Rafiyian
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Farzaneh Gouyandeh
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Saati
- Department of Nursing, Semnan Branch, Islamic Azad University, Semnan, Islamic Republic of Iran
| | - Amirhossein Davoodvandi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | | | - Reza Asemi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehran Sharifi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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10
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Fattahi M, Rezaee D, Fakhari F, Najafi S, Aghaei-Zarch SM, Beyranvand P, Rashidi MA, Bagheri-Mohammadi S, Zamani-Rarani F, Bakhtiari M, Bakhtiari A, Falahi S, Kenarkoohi A, Majidpoor J, Nguyen PU. microRNA-184 in the landscape of human malignancies: a review to roles and clinical significance. Cell Death Discov 2023; 9:423. [PMID: 38001121 PMCID: PMC10673883 DOI: 10.1038/s41420-023-01718-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 11/05/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023] Open
Abstract
MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) with a short length of 19-22 nucleotides. miRNAs are posttranscriptional regulators of gene expression involved in various biological processes like cell growth, apoptosis, and angiogenesis. miR-184 is a well-studied miRNA, for which most studies report its downregulation in cancer cells and tissues and experiments support its role as a tumor suppressor inhibiting malignant biological behaviors of cancer cells in vitro and in vivo. To exert its functions, miR-184 affects some signaling pathways involved in tumorigenesis like Wnt and β-catenin, and AKT/mTORC1 pathway, oncogenic factors (e.g., c-Myc) or apoptotic proteins, such as Bcl-2. Interestingly, clinical investigations have shown miR-184 with good performance as a prognostic/diagnostic biomarker for various cancers. Additionally, exogenous miR-184 in cell and xenograft animal studies suggest it as a therapeutic anticancer target. In this review, we outline the studies that evaluated the roles of miR-184 in tumorigenesis as well as its clinical significance.
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Affiliation(s)
- Mehdi Fattahi
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
- School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam
| | - Delsuz Rezaee
- School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran
| | - Fatemeh Fakhari
- Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Seyed Mohsen Aghaei-Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parisa Beyranvand
- Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
| | - Mohammad Amin Rashidi
- Student Research Committee, Department of Occupational Health and Safety, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeid Bagheri-Mohammadi
- Department of Physiology and Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Zamani-Rarani
- Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Abbas Bakhtiari
- Anatomical Sciences Department, Medical Faculty, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Shahab Falahi
- Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Azra Kenarkoohi
- Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran
- Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Jamal Majidpoor
- Department of Anatomy, Faculty of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - P U Nguyen
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
- School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam
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Pagoni M, Cava C, Sideris DC, Avgeris M, Zoumpourlis V, Michalopoulos I, Drakoulis N. miRNA-Based Technologies in Cancer Therapy. J Pers Med 2023; 13:1586. [PMID: 38003902 PMCID: PMC10672431 DOI: 10.3390/jpm13111586] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/02/2023] [Accepted: 11/04/2023] [Indexed: 11/26/2023] Open
Abstract
The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, making them appealing tools for novel therapeutic approaches. This review aims to discuss miRNA biogenesis and function, as well as highlight strategies for delivering miRNA agents, presenting viral, non-viral, and exosomic delivery as therapeutic approaches for different cancer types. We also consider the therapeutic role of microRNA-mediated drug repurposing in cancer therapy.
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Affiliation(s)
- Maria Pagoni
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
| | - Claudia Cava
- Department of Science, Technology and Society, University School for Advanced Studies IUSS Pavia, 27100 Pavia, Italy;
| | - Diamantis C. Sideris
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece;
| | - Margaritis Avgeris
- Laboratory of Clinical Biochemistry—Molecular Diagnostics, Second Department of Pediatrics, School of Medicine, “P. & A. Kyriakou” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Vassilios Zoumpourlis
- Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece;
| | - Ioannis Michalopoulos
- Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece;
| | - Nikolaos Drakoulis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
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12
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Sakalli-Tecim E, Gur-Dedeoglu B, Guray NT. Systems biology based miRNA-mRNA expression pattern analysis of Emodin in breast cancer cell lines. Pathol Res Pract 2023; 249:154780. [PMID: 37633004 DOI: 10.1016/j.prp.2023.154780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 07/20/2023] [Accepted: 08/21/2023] [Indexed: 08/28/2023]
Abstract
Breast cancer has been among the most prominent cancers with high mortality. Currently most of the offered therapeutics are toxic; hence, less toxic therapeutic intervention is required. Here, we studied the molecular mechanisms of the effect of a phytoestrogen Emodin on estrogen receptor positive MCF-7 and negative MDA-MB-231 cells by carrying out a comprehensive network assessment. Differentially expressed microRNAs along with their previously identified differentially expressed mRNAs were analyzed through microarrays by using integrative systems biology approach. For each cell line miRNA-target gene networks were built, gene ontology and pathway enrichment analyses were performed, enrichment maps were constructed and the potential key genes, miRNAs and miRNA-gene interactions were studied.
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Affiliation(s)
- Elif Sakalli-Tecim
- Department of Biotechnology, Middle East Technical University, Ankara, Turkiye
| | | | - N Tulin Guray
- Department of Biotechnology, Middle East Technical University, Ankara, Turkiye; Department of Biological Sciences, Middle East Technical University, Ankara, Turkiye.
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13
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Li X, Dai A, Tran R, Wang J. Text mining-based identification of promising miRNA biomarkers for diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1195145. [PMID: 37560309 PMCID: PMC10407569 DOI: 10.3389/fendo.2023.1195145] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 07/05/2023] [Indexed: 08/11/2023] Open
Abstract
Introduction MicroRNAs (miRNAs) are small, non-coding RNAs that play a critical role in diabetes development. While individual studies investigating the mechanisms of miRNA in diabetes provide valuable insights, their narrow focus limits their ability to provide a comprehensive understanding of miRNAs' role in diabetes pathogenesis and complications. Methods To reduce potential bias from individual studies, we employed a text mining-based approach to identify the role of miRNAs in diabetes and their potential as biomarker candidates. Abstracts of publications were tokenized, and biomedical terms were extracted for topic modeling. Four machine learning algorithms, including Naïve Bayes, Decision Tree, Random Forest, and Support Vector Machines (SVM), were employed for diabetes classification. Feature importance was assessed to construct miRNA-diabetes networks. Results Our analysis identified 13 distinct topics of miRNA studies in the context of diabetes, and miRNAs exhibited a topic-specific pattern. SVM achieved a promising prediction for diabetes with an accuracy score greater than 60%. Notably, miR-146 emerged as one of the critical biomarkers for diabetes prediction, targeting multiple genes and signal pathways implicated in diabetic inflammation and neuropathy. Conclusion This comprehensive approach yields generalizable insights into the network miRNAs-diabetes network and supports miRNAs' potential as a biomarker for diabetes.
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Affiliation(s)
- Xin Li
- Central Hospital Affiliated to Shandong First Medical University, Ophthalmology Department, Jinan, Shandong, China
| | - Andrea Dai
- Oakland University William Beaumont School of Medicine, Rochester, MI, United States
| | - Richard Tran
- University of Chicago, Master’s Program in Computer Science, Chicago, IL, United States
| | - Jie Wang
- Syracuse University, Applied Data Science Program, Syracuse, NY, United States
- MDSight, LLC, Brookeville, MD, United States
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14
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Hillyar CR, Kanabar SS, Pufal KR, Saw Hee JL, Lawson AW, Mohamed Y, Jasim D, Reed L, Rallis KS, Nibber A. A systematic review and meta-analysis of miRNAs for the detection of cervical cancer. Epigenomics 2023; 15:593-613. [PMID: 37535320 DOI: 10.2217/epi-2023-0183] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2023] Open
Abstract
Aim: This study aimed to critically appraise the evidence of the diagnostic effectiveness of miRNAs for the detection of cervical cancer. Methods & materials: A systematic review and meta-analysis was performed, searching PubMed, EMBASE and Web of Science. An umbrella meta-analysis of meta-analyses of individual biomarkers was performed. A Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment of evidence was also performed. Results: A total of 52 miRNAs were included. Umbrella meta-analysis revealed significant heterogeneity in terms of sensitivity, specificity, receiver operating characteristic (ROC), positive predictive value and/or negative predictive value. Umbrella effects were 0.76 (95% CI: 0.73-0.78), 0.78 (95% CI: 0.75-0.81), 0.77 (95% CI: 0.75-0.80), 0.75 (95% CI: 0.71-0.79) and 0.76 (95% CI: 0.74-0.79), respectively. Conclusion: Moderate quality evidence suggested miR199a-5p, miR21-5p and miR-141a had excellent diagnostic performance.
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Affiliation(s)
- Christopher Rt Hillyar
- Green Templeton College, University of Oxford, Oxford, OX2 6HG, UK
- Elderly Care, Royal Berkshire Hospital NHS Foundation Trust, Reading, RG1 5AN, UK
| | - Shivani S Kanabar
- General Surgery, Sandwell General Hospital, Sandwell & West Birmingham NHS Trust, West Bromwich, B71 4HJ, UK
| | - Kamil R Pufal
- General Surgery, Queens Hospital Burton, University Hospitals of Derby and Burton NHS Trust, Burton-on-Trent, DE13 0RB, UK
| | - Joshua Li Saw Hee
- Renal Unit, New Cross Hospital, The Royal Wolverhampton NHS Trust, Wolverhampton, WV10 0QP, UK
| | - Alexander W Lawson
- General Surgery, New Cross Hospital, The Royal Wolverhampton NHS Trust, Wolverhampton, WV10 0QP, UK
| | - Yethrib Mohamed
- General Surgery, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B9 5SS, UK
| | - Duha Jasim
- Intensive Care, Maidstone & Tunbridge Wells NHS Trust, Tunbridge Wells Hospital, Tunbridge Wells, TN2 4QJ, UK
| | - Lara Reed
- General Surgery, Weston General Hospital, University Hospitals Bristol and Weston NHS Foundation Trust, Weston-super-Mare, BS23 4TQ, UK
| | - Kathrine S Rallis
- Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
- Center for Hematology-Oncology, Barts Cancer Institute, Queen Mary University of London, London, EC1M 6AU, UK
| | - Anjan Nibber
- Green Templeton College, University of Oxford, Oxford, OX2 6HG, UK
- Nuffield Department of Population Health, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK
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15
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Yuan L, Jiang X, Gong Q, Gao N. Arsenic resistance protein 2 and microRNA biogenesis: Biological implications in cancer development. Pharmacol Ther 2023; 244:108386. [PMID: 36933704 DOI: 10.1016/j.pharmthera.2023.108386] [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: 01/01/2023] [Revised: 03/12/2023] [Accepted: 03/15/2023] [Indexed: 03/18/2023]
Abstract
Arsenic resistance protein 2 (Ars2) is a nuclear protein that plays a critical role in the regulation of microRNA (miRNA) biogenesis. Ars2 is required for cell proliferation and for the early stages of mammalian development through a possible effect on miRNA processing. Increasing evidence reveal that Ars2 is highly expressed in proliferating cancer cells, suggesting that Ars2 may be a potential therapeutic target for cancer. Therefore, development of the novel Ars2 inhibitors could represent the novel therapeutic strategies for treatment of cancer. In this review, we briefly discuss the mechanisms by which Ars2 regulates miRNA biogenesis and its impact on cell proliferation and cancer development. Particularly, we mainly discuss the role of Ars2 in the regulation of cancer development and highlight pharmacological targeting of Ars2 as a promising cancer therapeutic strategy.
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Affiliation(s)
- Liang Yuan
- Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563006, China
| | - Xiuxing Jiang
- College of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China
| | - Qihai Gong
- Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563006, China.
| | - Ning Gao
- Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563006, China.
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16
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Aggeletopoulou I, Mouzaki A, Thomopoulos K, Triantos C. miRNA Molecules-Late Breaking Treatment for Inflammatory Bowel Diseases? Int J Mol Sci 2023; 24:2233. [PMID: 36768556 PMCID: PMC9916785 DOI: 10.3390/ijms24032233] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/19/2023] [Accepted: 01/20/2023] [Indexed: 01/24/2023] Open
Abstract
MicroRNAs (miRNAs) are a group of non-coding RNAs that play a critical role in regulating epigenetic mechanisms in inflammation-related diseases. Inflammatory bowel diseases (IBDs), which primarily include ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic recurrent inflammation of intestinal tissues. Due to the multifactorial etiology of these diseases, the development of innovative treatment strategies that can effectively maintain remission and alleviate disease symptoms is a major challenge. In recent years, evidence for the regulatory role of miRNAs in the pathogenetic mechanisms of various diseases, including IBD, has been accumulating. In light of these findings, miRNAs represent potential innovative candidates for therapeutic application in IBD. In this review, we discuss recent findings on the role of miRNAs in regulating inflammatory responses, maintaining intestinal barrier integrity, and developing fibrosis in clinical and experimental IBD. The focus is on the existing literature, indicating potential therapeutic application of miRNAs in both preclinical experimental IBD models and translational data in the context of clinical IBD. To date, a large and diverse data set, which is growing rapidly, supports the potential use of miRNA-based therapies in clinical practice, although many questions remain unanswered.
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Affiliation(s)
- Ioanna Aggeletopoulou
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
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17
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de Los Reyes-García AM, Zapata-Martínez L, Águila S, Lozano ML, Martínez C, González-Conejero R. microRNAs as biomarkers of risk of major adverse cardiovascular events in atrial fibrillation. Front Cardiovasc Med 2023; 10:1135127. [PMID: 36895835 PMCID: PMC9988920 DOI: 10.3389/fcvm.2023.1135127] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
Atrial fibrillation is a complex and multifactorial disease. Although prophylactic anticoagulation has great benefits in avoiding comorbidities, adverse cardiovascular events still occur and thus in recent decades, many resources have been invested in the identification of useful markers in the prevention of the risk of MACE in these patients. As such, microRNAs, that are small non-coding RNAs whose function is to regulate gene expression post-transcriptionally, have a relevant role in the development of MACE. miRNAs, have been investigated for many years as potential non-invasive biomarkers of several diseases. Different studies have shown their utility in the diagnosis and prognosis of cardiovascular diseases. In particular, some studies have associated the presence of certain miRNAs in plasma with the development of MACE in AF. Despite these results, there are still many efforts to be done to allow the clinical use of miRNAs. The lack of standardization concerning the methodology in purifying and detecting miRNAs, still provides contradictory results. miRNAs also have a functional impact in MACE in AF through the dysregulation of immunothrombosis. Indeed, miRNAs may be a link between MACE and inflammation, through the regulation of neutrophil extracellular traps that are a key element in the establishment and evolution of thrombotic events. The use of miRNAs as therapy against thromboinflammatory processes should also be a future approach to avoid the occurrence of MACE in atrial fibrillation.
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Affiliation(s)
- Ascensión M de Los Reyes-García
- Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia IMIB Pascual Parrilla, Murcia, Spain
| | - Laura Zapata-Martínez
- Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia IMIB Pascual Parrilla, Murcia, Spain
| | - Sonia Águila
- Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia IMIB Pascual Parrilla, Murcia, Spain
| | - María L Lozano
- Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia IMIB Pascual Parrilla, Murcia, Spain
| | - Constantino Martínez
- Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia IMIB Pascual Parrilla, Murcia, Spain
| | - Rocío González-Conejero
- Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia IMIB Pascual Parrilla, Murcia, Spain
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18
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An HJ, Cho SH, Park HS, Kim JH, Kim YR, Lee WS, Lee JR, Joo SS, Ahn EH, Kim NK. Genetic Variations miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G and the Risk of Recurrent Pregnancy Loss in Korean Women. Biomedicines 2022; 10:biomedicines10102395. [PMID: 36289656 PMCID: PMC9598437 DOI: 10.3390/biomedicines10102395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 09/16/2022] [Accepted: 09/20/2022] [Indexed: 11/23/2022] Open
Abstract
This study investigated the genetic association between recurrent pregnancy loss (RPL) and microRNA (miRNA) polymorphisms in miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G in Korean women. Blood samples were collected from 381 RPL patients and 281 control participants, and genotyping of miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G was carried out by TaqMan miRNA RT-Real Time polymerase chain reaction (PCR). Four polymorphisms were identified, including miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G. MiR-10a dominant model (AA vs. AT + TT) and miR-499bGG genotypes were associated with increased RPL risk (adjusted odds ratio [AOR] = 1.520, 95% confidence interval [CI] = 1.038−2.227, p = 0.032; AOR = 2.956, 95% CI = 1.168−7.482, p = 0.022, respectively). Additionally, both miR-499 dominant (AA vs. AG + GG) and recessive (AA + AG vs. GG) models were significantly associated with increased RPL risk (AOR = 1.465, 95% CI = 1.062−2.020, p = 0.020; AOR = 2.677, 95% CI = 1.066−6.725, p = 0.036, respectively). We further propose that miR-10aA>T, miR-30cA>G, and miR-499bA>G polymorphisms effects could contribute to RPL and should be considered during RPL patient evaluation.
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Affiliation(s)
- Hui-Jeong An
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea
- College of Life Science, Gangneung-Wonju National University, Gangneung 25457, Korea
| | - Sung-Hwan Cho
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea
| | - Han-Sung Park
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea
| | - Ji-Hyang Kim
- Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13488, Korea
| | - Young-Ran Kim
- Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13488, Korea
| | - Woo-Sik Lee
- Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 06135, Korea
| | - Jung-Ryeol Lee
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam 13620, Korea
| | - Seong-Soo Joo
- College of Life Science, Gangneung-Wonju National University, Gangneung 25457, Korea
| | - Eun-Hee Ahn
- Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13488, Korea
- Correspondence: (E.-H.A.); (N.-K.K.)
| | - Nam-Keun Kim
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea
- Correspondence: (E.-H.A.); (N.-K.K.)
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19
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MINUTTI-ZANELLA C, BOJALIL-ÁLVAREZ L, GARCÍA-VILLASEÑOR E, LÓPEZ-MARTÍNEZ B, PÉREZ-TURRENT M, MURRIETA-ÁLVAREZ I, RUIZ-DELGADO GJ, ARGÜELLES GJRUIZ. miRNAs in multiple sclerosis: A clinical approach. Mult Scler Relat Disord 2022; 63:103835. [DOI: 10.1016/j.msard.2022.103835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 04/22/2022] [Accepted: 04/27/2022] [Indexed: 11/29/2022]
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20
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The Role of MicroRNAs in Hyperlipidemia: From Pathogenesis to Therapeutical Application. Mediators Inflamm 2022; 2022:3101900. [PMID: 35757107 PMCID: PMC9232323 DOI: 10.1155/2022/3101900] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/07/2022] [Indexed: 11/17/2022] Open
Abstract
Hyperlipidemia is a common metabolic disorder with high morbidity and mortality, which brings heavy burden on social. Understanding its pathogenesis and finding its potential therapeutic targets are the focus of current research in this field. In recent years, an increasing number of studies have proved that miRNAs play vital roles in regulating lipid metabolism and were considered as promising therapeutic targets for hyperlipidemia and related diseases. It is demonstrated that miR-191, miR-222, miR-224, miR-27a, miR-378a-3p, miR-140-5p, miR-483, and miR-520d-5p were closely associated with the pathogenesis of hyperlipidemia. In this review, we provide brief overviews about advances in miRNAs in hyperlipidemia and its potential clinical application value.
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21
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Yang G, Xiog Y, Wang G, Li W, Tang T, Sun J, Li J. miR‑374c‑5p regulates PTTG1 and inhibits cell growth and metastasis in hepatocellular carcinoma by regulating epithelial‑mesenchymal transition. Mol Med Rep 2022; 25:148. [PMID: 35234260 PMCID: PMC8915393 DOI: 10.3892/mmr.2022.12664] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 02/15/2022] [Indexed: 11/25/2022] Open
Abstract
A large number of studies have reported that microRNA (miR)-374c-5p plays an important role in the occurrence and development of malignant tumors, but there is no research on the role of miR-374c-5p in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of miR-374c-5p in HCC and the underlying molecular mechanism. The expression of miR-374c-5p in HCC tissues and HCC cell lines was analyzed via reverse transcription-quantitative PCR. The association between miR-374c-5p and clinical pathology was also analyzed in patients with HCC. Kaplan-Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR-374c-5p in HCC. The biological functions of miR-374c-5p, including cell proliferation, migration and invasion and its potential molecular mechanism were analyzed in vivo and in vitro. In addition, the molecular mechanism of miR-374c-5p in HCC was further explored. The results demonstrated that miR-374c-5p expression was lower in HCC than in matched adjacent tissue samples. Patients with low expression of miR-374c-5p had poor prognosis and short survival time. Overexpression of miR-374c-5p inhibited HCC cell proliferation, migration and invasion in vitro. In vivo, it was found that overexpression of miR-374c-5p significantly inhibited the growth and proliferation of HCC cells. Dual-luciferase reporter assays verified that miR-374c-5p directly targets the 3′-untranslated region of pituitary tumor-transforming 1 (PTTG1) and regulates PTTG1 expression. In general, it was revealed that miR-374c-5p regulates the malignant biological behavior of HCC through PTTG1, thereby affecting epithelial-mesenchymal transition. Thus, miR-374c-5p is a potential biological indicator to predict poor prognosis in patients with HCC.
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Affiliation(s)
- Gang Yang
- First Clinical Medical College, Jinan University, Tianhe, Guangzhou, Guangdong 510632, P.R. China
| | - Yongfu Xiog
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Guan Wang
- Physical Examination Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Weinan Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Tao Tang
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Ji Sun
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Jingdong Li
- First Clinical Medical College, Jinan University, Tianhe, Guangzhou, Guangdong 510632, P.R. China
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22
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Speer RM, Meaza I, Toyoda JH, Lu Y, Xu Q, Walter RB, Kong M, Lu H, Kouokam JC, Wise JP. Particulate hexavalent chromium alters microRNAs in human lung cells that target key carcinogenic pathways. Toxicol Appl Pharmacol 2022; 438:115890. [PMID: 35101437 PMCID: PMC8938933 DOI: 10.1016/j.taap.2022.115890] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 12/20/2021] [Accepted: 01/17/2022] [Indexed: 10/19/2022]
Abstract
Hexavalent chromium [Cr(VI)] is a global environmental pollutant and human lung carcinogen. However, the mechanisms of Cr(VI) carcinogenesis are not well defined. Cr(VI)-altered gene expression has been reported in the literature and is implicated in numerous mechanisms of Cr(VI) carcinogenesis. MicroRNAs (miRNAs) play a key role in controlling gene expression and are associated with carcinogenic mechanisms. To date no studies have evaluated global changes in miRNA expression in human cells after Cr(VI) exposure. We used RNA sequencing to evaluate how a particulate Cr(VI) compound (zinc chromate), the most potent form of Cr(VI), alters global miRNA expression after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 μg/cm2 zinc chromate in an immortalized, non-cancerous human lung cell line (WTHBF-6). Particulate Cr(VI) significantly affected expression of miRNAs at all time points and concentrations tested. We also found the number of significantly downregulated miRNAs increased in a time- and concentration-dependent manner and many miRNAs were upregulated after 24 h exposure at the intermediate concentration tested. Pathway analyses of the differentially expressed miRNAs predicted miRNAs target pathways of Cr(VI) carcinogenesis in a time- and concentration-dependent manner. These data are the first to evaluate global changes in miRNA expression in human lung cells after Cr(VI) exposure and indicate miRNAs may play a key role in pathways of Cr(VI) carcinogenesis.
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Affiliation(s)
- Rachel M. Speer
- Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA
| | - Idoia Meaza
- Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA
| | - Jennifer H. Toyoda
- Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA
| | - Yuan Lu
- Xiphophorus Genetic Stock Center, Texas State University, 601 University Dr. San Marcos, TX, USA
| | - Qian Xu
- Department of Bioinformatics and Biostatistics, University of Louisville, 485 E. Gray St., Louisville, KY, USA
| | - Ronald B. Walter
- Xiphophorus Genetic Stock Center, Texas State University, 601 University Dr. San Marcos, TX, USA
| | - Maiying Kong
- Department of Bioinformatics and Biostatistics, University of Louisville, 485 E. Gray St., Louisville, KY, USA
| | - Haiyan Lu
- Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA
| | - J. Calvin Kouokam
- Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA
| | - John Pierce Wise
- Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA.
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Expression Profile of miRs in Mesial Temporal Lobe Epilepsy: Systematic Review. Int J Mol Sci 2022; 23:ijms23020951. [PMID: 35055144 PMCID: PMC8781102 DOI: 10.3390/ijms23020951] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/08/2022] [Accepted: 01/12/2022] [Indexed: 02/04/2023] Open
Abstract
Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy in children and adults. TLE is characterized by variable onset and seizures. Moreover, this form of epilepsy is often resistant to pharmacotherapy. The search for new mechanisms for the development of TLE may provide us with a key to the development of new diagnostic methods and a personalized approach to the treatment. In recent years, the role of non-coding ribonucleic acids (RNA) has been actively studied, among which microRNA (miR) is of the greatest interest. (1) Background: The purpose of the systematic review is to analyze the studies carried out on the role of miRs in the development of mesial TLE (mTLE) and update the existing knowledge about the biomarkers of this disease. (2) Methods: The search for publications was carried out in the databases PubMed, Springer, Web of Science, Clinicalkeys, Scopus, OxfordPress, Cochrane. The search was carried out using keywords and combinations. We analyzed publications for 2016–2021, including original studies in an animal model of TLE and with the participation of patients with TLE, thematic and systemic reviews, and Cochrane reviews. (3) Results: this thematic review showed that miR‒155, miR‒153, miR‒361‒5p, miR‒4668‒5p, miR‒8071, miR‒197‒5p, miR‒145, miR‒181, miR‒199a, miR‒1183, miR‒129‒2‒3p, miR‒143‒3p (upregulation), miR–134, miR‒0067835, and miR‒153 (downregulation) can be considered as biomarkers of mTLE. However, the roles of miR‒146a, miR‒142, miR‒106b, and miR‒223 are questionable and need further study. (4) Conclusion: In the future, it will be possible to consider previously studied miRs, which have high specificity and sensitivity in mTLE, as prognostic biomarkers (predictors) of the risk of developing this disease in patients with potentially epileptogenic structural damage to the mesial regions of the temporal lobe of the brain (congenital disorders of the neuronal migration and neurogenesis, brain injury, neuro-inflammation, tumor, impaired blood supply, neurodegeneration, etc.).
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Abstract
MicroRNAs are RNAs of about 18-24 nucleotides in lengths, which are found in the small noncoding RNA class and have a crucial role in the posttranscriptional regulation of gene expression, cellular metabolic pathways, and developmental events. These small but essential molecules are first processed by Drosha and DGCR8 in the nucleus and then released into the cytoplasm, where they cleaved by Dicer to form the miRNA duplex. These duplexes are bound by the Argonaute (AGO) protein to form the RNA-induced silencing complex (RISC) in a process called RISC loading. Transcription of miRNAs, processing with Drosha and DGCR8 in the nucleus, cleavage by Dicer, binding to AGO proteins and forming RISC are the most critical steps in miRNA biogenesis. Additional molecules involved in biogenesis at these stages can enhance or inhibit these processes, which can radically change the fate of the cell. Biogenesis is regulated by many checkpoints at every step, primarily at the transcriptional level, in the nucleus, cytoplasm, with RNA regulation, RISC loading, miRNA strand selection, RNA methylation/uridylation, and turnover rate. Moreover, in recent years, different regulation mechanisms have been discovered in noncanonical Drosha or Dicer-independent pathways. This chapter seeks answers to how miRNA biogenesis and function are regulated through both canonical and non-canonical pathways.
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25
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Identification of human microRNAs targeting Pseudomonas aeruginosa genes by an in silico hybridization method. INFORMATICS IN MEDICINE UNLOCKED 2022. [DOI: 10.1016/j.imu.2022.101110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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26
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Wang X, Pham A, Kang L, Walker SA, Davidovich I, Iannotta D, TerKonda SP, Shapiro S, Talmon Y, Pham S, Wolfram J. Effects of Adipose-Derived Biogenic Nanoparticle-Associated microRNA-451a on Toll-like Receptor 4-Induced Cytokines. Pharmaceutics 2021; 14:16. [PMID: 35056912 PMCID: PMC8780819 DOI: 10.3390/pharmaceutics14010016] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/16/2021] [Accepted: 12/20/2021] [Indexed: 12/13/2022] Open
Abstract
Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs.
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Affiliation(s)
- Xinghua Wang
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA; (X.W.); (A.P.); (S.A.W.); (D.I.)
| | - Anthony Pham
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA; (X.W.); (A.P.); (S.A.W.); (D.I.)
| | - Lu Kang
- Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Sierra A. Walker
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA; (X.W.); (A.P.); (S.A.W.); (D.I.)
| | - Irina Davidovich
- Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute (RBNI), Technion-Israel Institute of Technology, Haifa 3200003, Israel; (I.D.); (Y.T.)
| | - Dalila Iannotta
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA; (X.W.); (A.P.); (S.A.W.); (D.I.)
| | - Sarvam P. TerKonda
- Department of Plastic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Shane Shapiro
- Center for Regenerative Medicine, Mayo Clinic, Jacksonville, FL 32224, USA;
- Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Yeshayahu Talmon
- Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute (RBNI), Technion-Israel Institute of Technology, Haifa 3200003, Israel; (I.D.); (Y.T.)
| | - Si Pham
- Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Joy Wolfram
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA; (X.W.); (A.P.); (S.A.W.); (D.I.)
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA
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Elkhodiry AA, El Tayebi HM. Scavenging the hidden impacts of non-coding RNAs in multiple sclerosis. Noncoding RNA Res 2021; 6:187-199. [PMID: 34938929 PMCID: PMC8666456 DOI: 10.1016/j.ncrna.2021.12.002] [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: 10/21/2021] [Revised: 12/03/2021] [Accepted: 12/05/2021] [Indexed: 11/30/2022] Open
Abstract
Multiple sclerosis (MS) is a chronic neuroinflammatory disease that causes severe neurological dysfunction leading to disabilities in patients. The prevalence of the disease has been increasing gradually worldwide, and the specific etiology behind the disease is not yet fully understood. Therapies aimed against treating MS patients have been growing lately, intending to delay the disease progression and increase the patients' quality of life. Various pathways play crucial roles in developing the disease, and several therapeutic approaches have been tackling those pathways. However, these strategies have shown several side effects and inconsistent efficacy. MicroRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) have been shown to act as key players in various disease pathogenesis and development. Several proinflammatory and anti-inflammatory miRNAs have been reported to participate in the development of MS. Hence, the review assesses the role of miRNAs, lncRNAs, and circRNAs in regulating immune cell functions better to understand their impact on the molecular mechanics of MS.
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Affiliation(s)
- Aya A. Elkhodiry
- Molecular Pharmacology Research Group, Department of Pharmacology, Toxicology and Clinical Pharmacy, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Hend M. El Tayebi
- Molecular Pharmacology Research Group, Department of Pharmacology, Toxicology and Clinical Pharmacy, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
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Manzano-Moreno FJ, Costela-Ruiz VJ, García-Recio E, Olmedo-Gaya MV, Ruiz C, Reyes-Botella C. Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma. Int J Mol Sci 2021; 22:12215. [PMID: 34830096 PMCID: PMC8624198 DOI: 10.3390/ijms222212215] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/06/2021] [Accepted: 11/10/2021] [Indexed: 12/14/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignant tumor worldwide. An early diagnosis can have a major positive impact on its prognosis. Human saliva contains cytokines, DNA and RNA molecules, circulating cells, and derivatives of tissues and extracellular vesicles, among other factors that can serve as biomarkers. Hence, the analysis of saliva may provide useful information for the early diagnosis of OSCC for its prognosis. The objective of this review was to determine the potential usefulness of salivary biomarkers (cytokines and microRNA) to diagnose OSCC and improve its prognosis. A combination of salivary miRNA and proteomic data could allow a definitive and early diagnosis to be obtained. However, there remains a need to optimize and standardize the protocols used to quantify miRNAs.
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Affiliation(s)
- Francisco Javier Manzano-Moreno
- Biomedical Group (BIO277), Department of Stomatology, School of Dentistry, University of Granada, 18071 Granada, Spain; (F.J.M.-M.); (C.R.-B.)
- Instituto Investigación Biosanitaria, ibs.Granada, 18071 Granada, Spain; (V.J.C.-R.); (E.G.-R.)
| | - Victor J. Costela-Ruiz
- Instituto Investigación Biosanitaria, ibs.Granada, 18071 Granada, Spain; (V.J.C.-R.); (E.G.-R.)
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, Campus de Ceuta, University of Granada, 51001 Ceuta, Spain
| | - Enrique García-Recio
- Instituto Investigación Biosanitaria, ibs.Granada, 18071 Granada, Spain; (V.J.C.-R.); (E.G.-R.)
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, Campus de Melilla, University of Granada, 52005 Melilla, Spain
| | | | - Concepción Ruiz
- Instituto Investigación Biosanitaria, ibs.Granada, 18071 Granada, Spain; (V.J.C.-R.); (E.G.-R.)
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain
- Institute of Neuroscience, University of Granada, 18071 Granada, Spain
| | - Candelaria Reyes-Botella
- Biomedical Group (BIO277), Department of Stomatology, School of Dentistry, University of Granada, 18071 Granada, Spain; (F.J.M.-M.); (C.R.-B.)
- Instituto Investigación Biosanitaria, ibs.Granada, 18071 Granada, Spain; (V.J.C.-R.); (E.G.-R.)
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Liu B, Shyr Y, Liu Q. Pan-Cancer Analysis Reveals Common and Specific Relationships between Intragenic miRNAs and Their Host Genes. Biomedicines 2021; 9:1263. [PMID: 34572448 PMCID: PMC8471046 DOI: 10.3390/biomedicines9091263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 11/21/2022] Open
Abstract
MicroRNAs (miRNAs) are small endogenous non-coding RNAs that play important roles in regulating gene expression. Most miRNAs are located within or close to genes (host). miRNAs and their host genes have either coordinated or independent transcription. We performed a comprehensive investigation on co-transcriptional patterns of miRNAs and host genes based on 4707 patients across 21 cancer types. We found that only 11.6% of miRNA-host pairs were co-transcribed consistently and strongly across cancer types. Most miRNA-host pairs showed a strong coexpression only in some specific cancer types, demonstrating a high heterogenous pattern. For two particular types of intergenic miRNAs, readthrough and divergent miRNAs, readthrough miRNAs showed higher coexpression with their host genes than divergent ones. miRNAs located within non-coding genes had tighter co-transcription with their hosts than those located within protein-coding genes, especially exonic and junction miRNAs. A few precursor miRNAs changed their dominate form between 5' and 3' strands in different cancer types, including miR-486, miR-99b, let-7e, miR-125a, let-7g, miR-339, miR-26a, miR-16, and miR-218, whereas only two miRNAs with multiple host genes switched their co-transcriptional partner in different cancer types (miR-219a-1 with SLC39A7/HSD17B8 and miR-3615 with RAB37/SLC9A3R1). miRNAs generated from distinct precursors (such as miR-125b from miR-125b-1 or miR-125b-2) were more likely to have cancer-dependent main contributors. miRNAs and hosts were less co-expressed in KIRC than other cancer types, possibly due to its frequent VHL mutations. Our findings shed new light on miRNA biogenesis and cancer diagnosis and treatments.
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Affiliation(s)
- Baohong Liu
- Key Laboratory of Veterinary Parasitology of Gansu Province, State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
| | - Yu Shyr
- Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Qi Liu
- Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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Plata-Bello J, Fariña-Jerónimo H, Betancor I, Salido E. High Expression of FOXP2 Is Associated with Worse Prognosis in Glioblastoma. World Neurosurg 2021; 150:e253-e278. [PMID: 33689847 DOI: 10.1016/j.wneu.2021.02.132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 02/27/2021] [Accepted: 02/28/2021] [Indexed: 02/08/2023]
Abstract
OBJECTIVE FOXP2 expression has been associated with the prognosis of some tumors, but the role of FOXP2 in glioblastoma remains unclear. The aim of the present work is to study the role of FOXP2 as a prognostic biomarker in glioblastoma. METHODS This is a retrospective observational case series study in which the expression of FOXP2 has been analyzed both at protein level (immunohistochemistry, n = 62) and at mRNA level (RNAseq, in a cohort of glioblastoma patients from The Cancer Genome Atlas [TCGA] database, n = 148). Other molecular and clinical data have also been included in the study, with special focus on miRNA expression data. Survival analysis using log-rank test and COX-regression have been used. Non-parametric statistical tests were also used to study differences between low and high FOXP2 expression groups. RESULTS Patients with a high expression of FOXP2 protein showed a worse prognosis than those patients with low expression in progression-free survival (hazard ratio 1.711; P = 0.034) and overall survival (hazard ratio 1.809; P = 0.014). These associations were still statistically significant in multivariate analysis. No prognostic association was found with FOXP2 RNA expression. Interestingly, 2 miRNAs that target FOXP2 (hsa-miR-181a-2-3p and hsa-miR-20a-3p) showed an interaction effect on overall survival with FOXP2 expression. A low level of these miRNA expression was associated with a significantly worse prognosis in patients with high FOXP2 RNA expression (log-rank test; P < 0.05). CONCLUSIONS Greater expression of FOXP2 at the protein level is associated with a worse prognosis. This protein expression may be regulated by the expression of specific miRNAs that target FOXP2 mRNA: hsa-miR-181a-2-3p and hsa-miR-20a-3p.
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Affiliation(s)
- Julio Plata-Bello
- Department of Neurosurgery, Hospital Universitario de Canarias, S/C de Tenerife, Spain.
| | - Helga Fariña-Jerónimo
- Department of Neurosurgery, Hospital Universitario de Canarias, S/C de Tenerife, Spain
| | - Isabel Betancor
- Department of Pathology, Hospital Universitario de Canarias, S/C de Tenerife, Spain
| | - Eduardo Salido
- Department of Pathology, Hospital Universitario de Canarias, S/C de Tenerife, Spain
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Horita M, Farquharson C, Stephen LA. The role of miR-29 family in disease. J Cell Biochem 2021; 122:696-715. [PMID: 33529442 PMCID: PMC8603934 DOI: 10.1002/jcb.29896] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 01/05/2021] [Accepted: 01/10/2021] [Indexed: 02/06/2023]
Abstract
MicroRNAs are small noncoding RNAs that can bind to the target sites in the 3’‐untranslated region of messenger RNA to regulate posttranscriptional gene expression. Increasing evidence has identified the miR‐29 family, consisting of miR‐29a, miR‐29b‐1, miR‐29b‐2, and miR‐29c, as key regulators of a number of biological processes. Moreover, their abnormal expression contributes to the etiology of numerous diseases. In the current review, we aimed to summarize the differential expression patterns and functional roles of the miR‐29 family in the etiology of diseases including osteoarthritis, osteoporosis, cardiorenal, and immune disease. Furthermore, we highlight the therapeutic potential of targeting members of miR‐29 family in these diseases. We present miR‐29s as promoters of osteoblast differentiation and apoptosis but suppressors of chondrogenic and osteoclast differentiation, fibrosis, and T cell differentiation, with clear avenues for therapeutic manipulation. Further research will be crucial to identify the precise mechanism of miR‐29 family in these diseases and their full potential in therapeutics.
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Affiliation(s)
- Masahiro Horita
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian, Scotland, UK
| | - Colin Farquharson
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian, Scotland, UK
| | - Louise A Stephen
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian, Scotland, UK
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Mansour SA, Farhat AA, Abd El-Zaher AH, Bediwy AS, Abdou SM, Al Saka AA, Zidan AAA. MicroRNA genetic signature in non-small cell lung cancer (NSCLC) Egyptian patients. THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2020. [DOI: 10.1186/s43168-020-00021-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Cancer development is associated with deregulated microRNA (miRNA) in body fluids including serum, plasma, and bronchoalveolar lavage (BAL). Early diagnosis and early treatment of lung cancer improve survival and response to treatment. So, finding an easy detectable biomarker is crucially important to improve the disease outcome. So, we analyzed the differential expression of miRNA using microarray both in serum and BAL of 37 non-small cell lung cancer (NSCLC) patients and 30 healthy control subjects (15 non-smokers and 15 smokers).
Results
A total of 32 miRNAs were significantly differentially expressed in serum of NSCLC patients versus controls (13 up-regulated and 19 down-regulated), whereas 14 miRNAs were significantly differentially expressed in BAL of NSCLC patients relative to control (12 upregulated and 2 downregulated). The accuracy of MiRNAs to detect lung cancer patients versus control was 94.3% with a specificity of 97.8% and a sensitivity of 92.3%.
Conclusions
Expression of miRNAs is specific in both serum and BAL of NSCLC patients, indicating that they might be considered easy diagnostic biomarkers for early lung cancer detection.
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Liu J, Han Y, Liu X, Wei S. Serum miR-185 Is a Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer. Technol Cancer Res Treat 2020; 19:1533033820973276. [PMID: 33251978 PMCID: PMC7705799 DOI: 10.1177/1533033820973276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE MicroRNAs (miRNAs) have been found to play important roles in the development of non-small cell lung carcinoma (NSCLC). The aim of this study was to analyze the expression and clinical value of serum miR-185 in NSCLC. METHODS Serum miR-185 levels were detected in 146 NSCLC patients, 50 patients with carcinoma in situ, 25 patients with non-malignant lung diseases (NMLD), and 80 healthy controls using quantitative reverse transcription PCR. The correlation between serum miR-185 level and clinical status of NSCLC was explored. RESULTS The results revealed that serum miR-185 expression was progressively decreased in healthy controls, patients with NMLD, patients with carcinoma in situ and NSCLC patients. In addition, compared to carcinoembryonic antigen (CEA), serum miR-185 demonstrated better diagnostic accuracy for discriminating patients with carcinoma from healthy controls, NSCLC patients from healthy controls and NSCLC patients from patients with carcinoma in situ. In addition, serum miR-185 levels were significantly elevated in post-treated samples compared to the pre-treated samples. Moreover, reduced serum miR-185 was closely associated with unfavorable clinicopathological parameters and worse survival. Univariate and multivariate cox regression analysis confirmed that serum miR-185 was an independent prognostic indicator for NSCLC. CONCLUSIONS Collectively, our findings have demonstrated that serum miR-185 might serve as a promising and robust biomarker for the early detection and prognosis prediction of NSCLC.
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Affiliation(s)
- Jinghao Liu
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin City, China
| | - Yueting Han
- Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin City, China
| | - Xingyu Liu
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin City, China
| | - Sen Wei
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin City, China
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Zhang J, Hadj-Moussa H, Storey KB. Marine periwinkle stress-responsive microRNAs: A potential factor to reflect anoxia and freezing survival adaptations. Genomics 2020; 112:4385-4398. [PMID: 32730984 DOI: 10.1016/j.ygeno.2020.07.036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 07/17/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022]
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Lee SH, Saadeldin IM. Exosomes as a Potential Tool for Supporting Canine Oocyte Development. Animals (Basel) 2020; 10:E1971. [PMID: 33121043 PMCID: PMC7693116 DOI: 10.3390/ani10111971] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 10/24/2020] [Accepted: 10/25/2020] [Indexed: 12/27/2022] Open
Abstract
The canine oviduct is a unique reproductive organ where the ovulated immature oocytes complete their maturation, while the other mammals ovulate matured gametes. Due to their peculiar reproductive characteristics, the in vitro maturation of dog oocytes is still not wellestablished compared with other mammals. Investigations of the microenvironment conditions in the oviductal canal are required to establish a reliable in vitro maturation system in the dog. Previous studies have suggested that the oviduct and its derivatives play a key role in improving fertilization as well as embryo development. In particular, the biological function of oviduct-derived exosomes on sperm and early embryo development has been investigated in porcine, bovine, and murine species. However, the information about their functions on canine cumulus-oocyte complexes is still elusive. Recent canine reproductive studies demonstrated how oviduct-derived extracellular vesicles such as microvesicles and exosomes interact with oocyte-cumulus complexes and how they can play roles in regulating canine cumulus/oocyte communications. In this review, we summarize the physiological characteristics of canine oviduct-derived exosomes and their potential effects on cumulus cells development as well as oocyte in vitro maturation via molecular signaling pathways.
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Affiliation(s)
- Seok Hee Lee
- Center for Reproductive Sciences, Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, CA 94143, USA
| | - Islam M. Saadeldin
- Department of Animal Production, College of Food and Agriculture Sciences, King Saud University, Riyadh 44511, Saudi Arabia;
- Department of Comparative Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
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Long non-coding RNA HOTAIRM1 promotes proliferation and inhibits apoptosis of glioma cells by regulating the miR-873-5p/ZEB2 axis. Chin Med J (Engl) 2020; 133:174-182. [PMID: 31929367 PMCID: PMC7028173 DOI: 10.1097/cm9.0000000000000615] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background Glioblastoma is one of the most common malignant brain tumors. Conventional clinical treatment of glioblastoma is not sufficient, and the molecular mechanism underlying the initiation and development of this disease remains unclear. Our study aimed to explore the expression and function of miR-873a-5p in glioblastoma and related molecular mechanism. Methods We analyzed the most dysregulated microRNAs from the Gene Expression Omnibus (GEO) database and examined the expression of miR-873-5p in 20 glioblastoma tissues compared with ten normal brain tissues collected in the Zhejiang Tongde Hospital. We then overexpressed or inhibited miR-873-5p expression in U87 glioblastoma cell lines and analyzed the phenotype using the cell counting kit-8 assay, wound healing assay, and apoptosis. In addition, we predicted upstream and downstream genes of miR-873-5p in glioblastoma using bioinformatics analysis and tested our hypothesis in U87 cells using the luciferase reporter gene assay and Western blotting assay. The differences between two groups were analyzed by Student's t test. The Kruskal-Wallis test was used for the comparison of multiple groups. A P < 0.05 was considered to be significant. Results The miR-873-5p was downregulated in glioblastoma tissues compared with that in normal brain tissues (normal vs. tumor, 0.762 ± 0.231 vs. 0.378 ± 0.114, t = 4.540, P < 0.01). Overexpression of miR-873-5p inhibited cell growth (t = 6.095, P < 0.01) and migration (t = 3.142, P < 0.01) and promoted cell apoptosis (t = 4.861, P < 0.01), while inhibition of miR-873-5p had the opposite effect. Mechanistically, the long non-coding RNA HOTAIRM1 was found to act as a sponge of miR-873-5p to activate ZEB2 expression in U87 cells. Conclusions We uncovered a novel HOTAIRM1/miR-873-5p/ZEB2 axis in glioblastoma cells, providing new insight into glioblastoma progression and a theoretical basis for the treatment of glioblastoma.
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Włodarski A, Strycharz J, Wróblewski A, Kasznicki J, Drzewoski J, Śliwińska A. The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress. Int J Mol Sci 2020; 21:ijms21186902. [PMID: 32962281 PMCID: PMC7555602 DOI: 10.3390/ijms21186902] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023] Open
Abstract
Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.
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Affiliation(s)
- Adam Włodarski
- Department of Internal Diseases, Diabetology and Clinical Pharmacology, Medical University of Lodz, 92-213 Lodz, Poland;
- Correspondence: (A.W.); (J.S.); (A.Ś.)
| | - Justyna Strycharz
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland;
- Correspondence: (A.W.); (J.S.); (A.Ś.)
| | - Adam Wróblewski
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland;
| | - Jacek Kasznicki
- Department of Internal Diseases, Diabetology and Clinical Pharmacology, Medical University of Lodz, 92-213 Lodz, Poland;
| | - Józef Drzewoski
- Central Teaching Hospital of the Medical University of Lodz, 92-213 Lodz, Poland;
| | - Agnieszka Śliwińska
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
- Correspondence: (A.W.); (J.S.); (A.Ś.)
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Desvignes T, Loher P, Eilbeck K, Ma J, Urgese G, Fromm B, Sydes J, Aparicio-Puerta E, Barrera V, Espín R, Thibord F, Bofill-De Ros X, Londin E, Telonis AG, Ficarra E, Friedländer MR, Postlethwait JH, Rigoutsos I, Hackenberg M, Vlachos IS, Halushka MK, Pantano L. Unification of miRNA and isomiR research: the mirGFF3 format and the mirtop API. Bioinformatics 2020; 36:698-703. [PMID: 31504201 DOI: 10.1093/bioinformatics/btz675] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 07/17/2019] [Accepted: 08/28/2019] [Indexed: 02/07/2023] Open
Abstract
MOTIVATION MicroRNAs (miRNAs) are small RNA molecules (∼22 nucleotide long) involved in post-transcriptional gene regulation. Advances in high-throughput sequencing technologies led to the discovery of isomiRs, which are miRNA sequence variants. While many miRNA-seq analysis tools exist, the diversity of output formats hinders accurate comparisons between tools and precludes data sharing and the development of common downstream analysis methods. RESULTS To overcome this situation, we present here a community-based project, miRNA Transcriptomic Open Project (miRTOP) working towards the optimization of miRNA analyses. The aim of miRTOP is to promote the development of downstream isomiR analysis tools that are compatible with existing detection and quantification tools. Based on the existing GFF3 format, we first created a new standard format, mirGFF3, for the output of miRNA/isomiR detection and quantification results from small RNA-seq data. Additionally, we developed a command line Python tool, mirtop, to create and manage the mirGFF3 format. Currently, mirtop can convert into mirGFF3 the outputs of commonly used pipelines, such as seqbuster, isomiR-SEA, sRNAbench, Prost! as well as BAM files. Some tools have also incorporated the mirGFF3 format directly into their code, such as, miRge2.0, IsoMIRmap and OptimiR. Its open architecture enables any tool or pipeline to output or convert results into mirGFF3. Collectively, this isomiR categorization system, along with the accompanying mirGFF3 and mirtop API, provide a comprehensive solution for the standardization of miRNA and isomiR annotation, enabling data sharing, reporting, comparative analyses and benchmarking, while promoting the development of common miRNA methods focusing on downstream steps of miRNA detection, annotation and quantification. AVAILABILITY AND IMPLEMENTATION https://github.com/miRTop/mirGFF3/ and https://github.com/miRTop/mirtop. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- Thomas Desvignes
- Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA
| | - Phillipe Loher
- Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA 19144, USA
| | - Karen Eilbeck
- University of Utah, Biomedical Informatics, Salt Lake City, UT 84108, USA
| | - Jeffery Ma
- Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA 19144, USA
| | - Gianvito Urgese
- Department of Control and Computer Engineering, Politecnico di Torino, Torino 10129, Italy
| | - Bastian Fromm
- Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 114 18, Sweden
| | - Jason Sydes
- Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA
| | - Ernesto Aparicio-Puerta
- Computational Epigenomics Laboratory, Genetics Department and Biotechnology Institute and Biosanitary Institute, University of Granada, Granada 18002, Spain
| | - Victor Barrera
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Roderic Espín
- Universitat Oberta de Catalunya, Barcelona 08018, Spain
| | - Florian Thibord
- Sorbonne Université, Pierre Louis Doctoral School of Public Health, Paris 75006, France.,Institut National pour la Santé et la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMR_S), University of Bordeaux, Bordeaux 33076, France
| | - Xavier Bofill-De Ros
- RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
| | - Eric Londin
- Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA 19144, USA
| | - Aristeidis G Telonis
- Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA 19144, USA
| | - Elisa Ficarra
- Department of Control and Computer Engineering, Politecnico di Torino, Torino 10129, Italy
| | - Marc R Friedländer
- Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 114 18, Sweden
| | | | - Isidore Rigoutsos
- Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA 19144, USA
| | - Michael Hackenberg
- Computational Epigenomics Laboratory, Genetics Department and Biotechnology Institute and Biosanitary Institute, University of Granada, Granada 18002, Spain
| | - Ioannis S Vlachos
- Non-coding Research Lab, Department of Pathology, Cancer Research Institute, Harvard Medical School Initiative for RNA Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
| | - Marc K Halushka
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Lorena Pantano
- Bioinformatics Core, The Picower Institute for Learning and Memory, Cambridge, MA 02139, USA
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Cao J, Da Y, Li H, Peng Y, Hu X. Upregulation of microRNA-451 attenuates myocardial I/R injury by suppressing HMGB1. PLoS One 2020; 15:e0235614. [PMID: 32678819 PMCID: PMC7367451 DOI: 10.1371/journal.pone.0235614] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Accepted: 06/19/2020] [Indexed: 12/22/2022] Open
Abstract
Both MicroRNAs and HMGB1 took part in pathological process of myocardial I/R injury though several signaling pathways. We hypothesized that mircoRNA451 (miR-451), a group of small non-coding RNAs, could improve this injury by inhibiting HMGB1. Male SD rats were randomly distributed into 5 groups and subjected to I/R process. After 24 hours of reperfusion injury, the serum content of CK and LDH, the content of MDA in tissue and activity of SOD were detected; The infarcted areas were defined by TTC staining and Evans Blue; TUNEL staining and cleaved-Caspase 3 were used to test apoptosis; HMGB1 was detected by real-time fluorescence quantitative PCR and Western Blotting. Compared with the I/R and I/R+Ad-GFP group, upregulation of miR-451 could reduce the infarcted areas, cardiomyocytes apoptosis index, expression of cleaved-caspase 3 and content of CK and LDH significantly(P<0.05); Meanwhile, upregulation of miR-451 could also obviously inhibit HMGB1, the increase of MDA and the decrease of SOD (P<0.05). So this study revealed that upregulation of miR-451 could prevent myocardial I/R injury by suppressing HMGB1.
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Affiliation(s)
- Jianlei Cao
- Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China
| | - Yurong Da
- School of Medicine, Jianghan University, Wuhan, P.R. China
| | - Hang Li
- Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China
| | - Yuanyuan Peng
- Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China
| | - Xiaorong Hu
- Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China
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Böhm A, Vachalcova M, Snopek P, Bacharova L, Komarova D, Hatala R. Molecular Mechanisms, Diagnostic Aspects and Therapeutic Opportunities of Micro Ribonucleic Acids in Atrial Fibrillation. Int J Mol Sci 2020; 21:ijms21082742. [PMID: 32326592 PMCID: PMC7215603 DOI: 10.3390/ijms21082742] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 04/13/2020] [Accepted: 04/13/2020] [Indexed: 12/22/2022] Open
Abstract
Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules responsible for regulation of gene expression. They are involved in many pathophysiological processes of a wide spectrum of diseases. Recent studies showed their involvement in atrial fibrillation. They seem to become potential screening biomarkers for atrial fibrillation and even treatment targets for this arrhythmia. The aim of this review article was to summarize the latest knowledge about miRNA and their molecular relation to the pathophysiology, diagnosis and treatment of atrial fibrillation.
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Affiliation(s)
- Allan Böhm
- National Cardiovascular Institute, 831 01 Bratislava, Slovakia;
- Faculty of Medicine, Slovak Medical University, 831 01 Bratislava, Slovakia
- Academy—Research Organization, 811 02 Bratislava, Slovakia; (M.V.); (P.S.); (D.K.)
- Correspondence:
| | - Marianna Vachalcova
- Academy—Research Organization, 811 02 Bratislava, Slovakia; (M.V.); (P.S.); (D.K.)
- East-Slovak Institute of Cardiovascular Diseases, 040 11 Kosice, Slovakia
| | - Peter Snopek
- Academy—Research Organization, 811 02 Bratislava, Slovakia; (M.V.); (P.S.); (D.K.)
- Cardiology Clinic Faculty Hospital, 950 01 Nitra, Slovakia
- Saint Elisabeth University of Health and Social work, 811 02 Bratislava, Slovakia
| | - Ljuba Bacharova
- Faculty of Medicine, Comenius University, 813 72 Bratislava, Slovakia;
- International Laser Center, 841 04 Bratislava, Slovakia
| | - Dominika Komarova
- Academy—Research Organization, 811 02 Bratislava, Slovakia; (M.V.); (P.S.); (D.K.)
| | - Robert Hatala
- National Cardiovascular Institute, 831 01 Bratislava, Slovakia;
- Faculty of Medicine, Slovak Medical University, 831 01 Bratislava, Slovakia
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Cho SH, Kim YR, Kim JH, An HJ, Kim JO, Ko JJ, Lee WS, Kim NK. The association of miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T polymorphisms with a risk of primary ovarian insufficiency in Korean women. Menopause 2020; 26:409-416. [PMID: 30422934 DOI: 10.1097/gme.0000000000001258] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The purpose of this study was to investigate the association of microRNA polymorphisms (miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T) with primary ovarian insufficiency (POI) in Korean women. METHODS We conducted a case-control study of Korean women: 142 participants with POI and 266 controls with at least 1 live birth and no history of pregnancy loss. RESULTS The haplotype-based multifactor dimensionality reduction analysis revealed that the T-C-T-G (miR-25/-32/-125/-222), T-A-C-G (miR-25/-32/-125/-222), C-T-G (miR-32/-125/-222), A-C-G (miR-32/-125/-222), T-G (miR-122/-222), C-T (miR-32/-125), and C-C (miR-25/-32) inferred haplotypes were significantly less frequent in POI (P < 0.05), which suggested potential protective effects. Participants with POI had significantly increased luteinizing hormone levels (P < 0.05), but hormonal levels, including luteinizing hormone, were not significantly different between POI women and control women with miR-32/-125/-222. CONCLUSIONS After considering multiple comparisons, we concluded that miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T had no relation with POI.
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Affiliation(s)
- Sung Hwan Cho
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Korea
| | - Young Ran Kim
- Department of Obstetrics and Gynecology, School of Medicine, CHA University, Seongnam, Korea
| | - Ji Hyang Kim
- Department of Obstetrics and Gynecology, School of Medicine, CHA University, Seongnam, Korea
| | - Hui Jeong An
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Korea
| | - Jung Oh Kim
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Korea
| | - Jung Jae Ko
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Korea
| | - Woo Sik Lee
- Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Nam Keun Kim
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Korea
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Bhat AA, Younes SN, Raza SS, Zarif L, Nisar S, Ahmed I, Mir R, Kumar S, Sharawat SK, Hashem S, Elfaki I, Kulinski M, Kuttikrishnan S, Prabhu KS, Khan AQ, Yadav SK, El-Rifai W, Zargar MA, Zayed H, Haris M, Uddin S. Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance. Mol Cancer 2020; 19:57. [PMID: 32164715 PMCID: PMC7069174 DOI: 10.1186/s12943-020-01175-9] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 03/02/2020] [Indexed: 12/12/2022] Open
Abstract
Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.
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Affiliation(s)
- Ajaz A Bhat
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Salma N Younes
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | - Lubna Zarif
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Sabah Nisar
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Ikhlak Ahmed
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Rashid Mir
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Sachin Kumar
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Surender K Sharawat
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Sheema Hashem
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Imadeldin Elfaki
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Michal Kulinski
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Shilpa Kuttikrishnan
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Kirti S Prabhu
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Abdul Q Khan
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Santosh K Yadav
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Wael El-Rifai
- Department of Surgery, University of Miami, Miami, Florida, USA
| | - Mohammad A Zargar
- Department of Biotechnology, Central University of Kashmir, Ganderbal, Jammu and Kashmir, India
| | - Hatem Zayed
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Mohammad Haris
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar.
- Laboratory Animal Research Center, Qatar University, Doha, Qatar.
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
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Jang HY, Lim SM, Lee HJ, Hong JS, Kim GJ. Identification of microRNAs and their target genes in the placenta as biomarkers of inflammation. Clin Exp Reprod Med 2020; 47:42-53. [PMID: 32146774 PMCID: PMC7127901 DOI: 10.5653/cerm.2019.03013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 09/18/2019] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE Recently, microRNA (miRNA) has been identified both as a powerful regulator involved in various biological processes through the regulation of numerous genes and as an effective biomarker for the prediction and diagnosis of various disease states. The objective of this study was to identify and validate miRNAs and their target genes involved in inflammation in placental tissue. METHODS Microarrays were utilized to obtain miRNA and gene expression profiles from placentas with or without inflammation obtained from nine normal pregnant women and 10 preterm labor patients. Quantitative real-time polymerase chain reaction and Western blots were performed to validate the miRNAs and differentially-expressed genes in the placentas with inflammation. Correlations between miRNA and target gene expression were confirmed by luciferase assays in HTR-8/SVneo cells. RESULTS We identified and validated miRNAs and their target genes that were differentially expressed in placentas with inflammation. We also demonstrated that several miRNAs (miR-371a-5p, miR-3065-3p, miR-519b-3p, and miR-373-3p) directly targeted their target genes (LEF1, LOX, ITGB4, and CD44). However, some miRNAs and their direct target genes showed no correlation in tissue samples. Interestingly, miR-373-3p and miR-3065-3p were markedly regulated by lipopolysaccharide (LPS) treatment, although the expression of their direct targets CD44 and LOX was not altered by LPS treatment. CONCLUSION These results provide candidate miRNAs and their target genes that could be used as placental biomarkers of inflammation. These candidates may be useful for further miRNA-based biomarker development.
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Affiliation(s)
- Hee Yeon Jang
- Department of Biomedical Science, CHA University, Seongnam, Korea
| | - Seung Mook Lim
- Department of Biomedical Science, CHA University, Seongnam, Korea
| | - Hyun Jung Lee
- Non-Clinical Evaluation Center, CHA Advanced Research Institute, Seongnam, Korea
| | - Joon-Seok Hong
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Gi Jin Kim
- Department of Biomedical Science, CHA University, Seongnam, Korea
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Behl T, Kumar C, Makkar R, Gupta A, Sachdeva M. Intercalating the Role of MicroRNAs in Cancer: As Enemy or Protector. Asian Pac J Cancer Prev 2020; 21:593-598. [PMID: 32212783 PMCID: PMC7437313 DOI: 10.31557/apjcp.2020.21.3.593] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Indexed: 12/18/2022] Open
Abstract
Objective: The transformation in cells at genetic levels stimulatesthe proliferation of cancer. The current review highlights the role of miRNA in management of cancer by altering processes of body at cellular levels. Methods: A deep research on the literature available till date for miRNA in cancer was conducted using various medical sites like PubMed, MEDLINE from internet and data was collected. The articles were majorly preferred in English language. Results: The development of normal cells into cancerous cells is a multivalent procedure highlighting numerous responsible factors. During the progression of cancer, the role of oncogene and tumor suppressor genes outshines at different levels of tumorogenesis. Metastasis poses highest threat in cancer progression and fabricates obstacles to clinicians and researchers in preventing formation of tumor on secondary sites. The mesenchymal-epithelial transition (MET) and epithelial mesenchymal transition (EMT) induce dissemination and ultimately progression of cancer. Conclusion: A comprehensive knowledge of the altered genes and the mechanism by which they induce formation of tumor is essential as they contribute in proliferating cancer at various stages, aggravating clinical symptoms. Hence miRNAs can be efficiently employed as an emerging treatment therapy for cancer.
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Affiliation(s)
- Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Chanchal Kumar
- Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
| | - Rashita Makkar
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Amit Gupta
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
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Wu B, Liu G, Jin Y, Yang T, Zhang D, Ding L, Zhou F, Pan Y, Wei Y. miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2. Front Oncol 2020; 10:108. [PMID: 32175269 PMCID: PMC7054484 DOI: 10.3389/fonc.2020.00108] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 01/21/2020] [Indexed: 12/24/2022] Open
Abstract
MicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effects and their mechanisms in breast cancer using both in vitro and in vivo experiments. This study showed that miR-15b-5p expression was upregulated in breast cancer compared with normal breast tissue and was positively correlated with poor overall survival in patients. Knockdown of miR-15b-5p in MCF-7 and MD-MBA-231 breast cancer cells restrained cell growth and invasiveness and induced apoptosis, whereas overexpression of miR-15b-5p achieved the opposite effects. We next revealed a negative correlation between miR-15b-5p and heparanase-2 (HPSE2) expression in breast cancer. Knockdown of miR-15b-5p significantly increased HPSE2 expression at both mRNA and protein levels in breast cancer cells in vitro. The underlying mechanisms of miR-15-5p in breast cancer were investigated using luciferase activity reporter assay and rescue experiments. In addition, miR-15b-5p knockdown significantly inhibited tumor growth in a xenograft model in mice. In summary, we showed that miR-15b-5p promotes breast cancer cell proliferation, migration, and invasion by directly targeting HPSE2. Accordingly, miR-15b-5p may serve both as a tool for prognosis and as a target for therapy of breast cancer patients.
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Affiliation(s)
- Balu Wu
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Guohong Liu
- Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Yanxia Jin
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Tian Yang
- Department of Clinical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Dongdong Zhang
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Lu Ding
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Fuling Zhou
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Yunbao Pan
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Yongchang Wei
- Hubei Key Laboratory of Tumor Biological Behaviors, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
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Moghadasi M, Alivand M, Fardi M, Moghadam KS, Solali S. Emerging molecular functions of microRNA-124: Cancer pathology and therapeutic implications. Pathol Res Pract 2020; 216:152827. [PMID: 31983567 DOI: 10.1016/j.prp.2020.152827] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 12/22/2019] [Accepted: 01/18/2020] [Indexed: 12/23/2022]
Abstract
MicroRNAs are characterized as small, single-stranded, non-coding RNA molecules that bind to their target mRNA to prevent protein synthesis. MicroRNAs regulate various normal processes; however, they are aberrantly regulated in many cancers. They control the expression of various genes, including cancer-related genes. This causes microRNAs to be considered as a good target for further investigations for designing novel therapeutic strategies. Since miR124 is known for some time already, it has a tumor-suppressing role in various cancers. Numerous studies indicate its definite roles in malignant processes such as epithelial-to-mesenchymal transition, cell cycle arrest, metastasis, cancer stem cell formation and induction of apoptosis. However, some studies have indicated a dual role for miR-124 in oncogenic processes like autophagy and multi-drug resistance. In this article, we will review recent researches on the biological functions and clinical implications of miR-124. Subsequently, we will discuss future perspectives in terms of the roles of this miRNA in cancers.
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Affiliation(s)
- Maryam Moghadasi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammadreza Alivand
- Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoumeh Fardi
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Saeed Solali
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Division of Hematology and Transfusion Medicine, Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Kapodistrias N, Theocharopoulou G, Vlamos P. A Hypothesis of Circulating MicroRNAs' Implication in High Incidence of Atrial Fibrillation and Other Electrocardiographic Abnormalities in Cancer Patients. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1196:1-9. [PMID: 32468302 DOI: 10.1007/978-3-030-32637-1_1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
MicroRNAs are short non-coding RNA molecules that control posttranscriptional gene expression and are present in tissues cells but also circulate in biological fluids in various forms (exosome, connected with proteins, apoptotic bodies, etc.). The roles that circulated extracellular serum microRNAs possess in cancer development, like in the delivery from a recipient cell to distant tissues and the repression of host genes resulting in the impairment of critical functions, are still undetermined. Disturbances, such as the higher incidence of atrial fibrillation in cancer patients, could be analyzed in the frame of suppressive action of circulated microRNAs in genes that control cardiac conduction in atrium. More precisely, mir-21 overexpression in tissues promotes atrium fibrosis and impairs conductibility. A possible hypothesis is that the high levels of circulating microRNA in cancer may exert the same effect. Further experiments are necessary to corroborate the hypothesis.
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Cristaldi M, Mauceri R, Di Fede O, Giuliana G, Campisi G, Panzarella V. Salivary Biomarkers for Oral Squamous Cell Carcinoma Diagnosis and Follow-Up: Current Status and Perspectives. Front Physiol 2019; 10:1476. [PMID: 31920689 PMCID: PMC6914830 DOI: 10.3389/fphys.2019.01476] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 11/18/2019] [Indexed: 12/22/2022] Open
Abstract
Oral cancer is the sixth most common cancer type in the world, and 90% of it is represented by oral squamous cell carcinoma (OSCC). Despite progress in preventive and therapeutic strategies, delay in OSCC diagnosis remains one of the major causes of high morbidity and mortality; indeed the majority of OSCC has been lately identified in the advanced clinical stage (i.e., III or IV). Moreover, after primary treatment, recurrences and/or metastases are found in more than half of the patients (80% of cases within the first 2 years) and the 5-year survival rate is still lower than 50%, resulting in a serious issue for public health. Currently, histological investigation represents the "gold standard" of OSCC diagnosis; however, recent studies have evaluated the potential use of non-invasive methods, such as "liquid biopsy," for the detection of diagnostic and prognostic biomarkers in body fluids of oral cancer patients. Saliva is a biofluid containing factors such as cytokines, DNA and RNA molecules, circulating and tissue-derived cells, and extracellular vesicles (EVs) that may be used as biomarkers; their analysis may give us useful information to do early diagnosis of OSCC and improve the prognosis. Therefore, the aim of this review is reporting the most recent data on saliva biomarker detection in saliva liquid biopsy from oral cancer patients, with particular attention to circulating tumor DNA (ctDNA), EVs, and microRNAs (miRNAs). Our results highlight that saliva liquid biopsy has several promising clinical uses in OSCC management; it is painless, accessible, and low cost and represents a very helpful source of diagnostic and prognostic biomarker detection. Even if standardized protocols for isolation, characterization, and evaluation are needed, recent data suggest that saliva may be successfully included in future clinical diagnostic processes, with a considerable impact on early treatment strategies and a favorable outcome.
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Affiliation(s)
- Marta Cristaldi
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Rodolfo Mauceri
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
| | - Olga Di Fede
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Giovanna Giuliana
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Giuseppina Campisi
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Vera Panzarella
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
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Circulating MicroRNAs as Prognostic Molecular Biomarkers in Human Head and Neck Cancer: A Systematic Review and Meta-Analysis. DISEASE MARKERS 2019; 2019:8632018. [PMID: 31827646 PMCID: PMC6885815 DOI: 10.1155/2019/8632018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 09/08/2019] [Accepted: 10/21/2019] [Indexed: 01/02/2023]
Abstract
Background Circulating microRNAs (miRNAs) are potential molecular biomarkers for cancer detection; however, little is known about their prognostic role in head and neck cancer. This current study is aimed at evaluating the role of novel miRNAs in the survival of head and neck cancer patients. Materials and Methods We performed a systematic literature search using online databases for articles published between December 2006 and February 2019. A meta-analysis was conducted to assess the correlation between miRNA expressions and overall survival (OS) among the selected head and neck cancer studies. After multilevel screening by reviewers, meta-analysis was performed using hazard ratios (HR) and associated 95% confidence interval (CI) of survival to calculate a pooled effect size. Result A total of 1577 patients across 13 studies were included in the literature review, with 18 miRNAs upregulated and 4 miRNAs downregulated predicting a poor overall survival. The forest plot generated using cumulated survival data resulted in a pooled HR value of 2.943 (95% CI: 2.394-3.618) indicating a strong association of dysregulated miRNA expression with a poor outcome. Only 2 miRNAs—low levels of miR-9 and high levels of miR-483-5p—were observed in two studies, both showing a significant association with overall cancer survival. Conclusion To our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the prognostic role of circulating miRNAs from blood in head and neck cancer patients. The combined effect estimates a HR across multiple studies and also supports the previous individual findings that an alteration in miRNA expression is highly associated with poor prognosis. This has the potential to use serum and/or plasma miRNAs as biomarkers and become novel tools for predicting the prognosis of head and neck cancer patients in the near future.
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50
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Tsegay PS, Lai Y, Liu Y. Replication Stress and Consequential Instability of the Genome and Epigenome. Molecules 2019; 24:molecules24213870. [PMID: 31717862 PMCID: PMC6864812 DOI: 10.3390/molecules24213870] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 10/25/2019] [Accepted: 10/25/2019] [Indexed: 12/12/2022] Open
Abstract
Cells must faithfully duplicate their DNA in the genome to pass their genetic information to the daughter cells. To maintain genomic stability and integrity, double-strand DNA has to be replicated in a strictly regulated manner, ensuring the accuracy of its copy number, integrity and epigenetic modifications. However, DNA is constantly under the attack of DNA damage, among which oxidative DNA damage is the one that most frequently occurs, and can alter the accuracy of DNA replication, integrity and epigenetic features, resulting in DNA replication stress and subsequent genome and epigenome instability. In this review, we summarize DNA damage-induced replication stress, the formation of DNA secondary structures, peculiar epigenetic modifications and cellular responses to the stress and their impact on the instability of the genome and epigenome mainly in eukaryotic cells.
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Affiliation(s)
- Pawlos S. Tsegay
- Biochemistry Ph.D. Program, Florida International University, Miami, FL 33199, USA;
| | - Yanhao Lai
- Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA;
- Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA
| | - Yuan Liu
- Biochemistry Ph.D. Program, Florida International University, Miami, FL 33199, USA;
- Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA;
- Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA
- Correspondence:
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