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1
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Jia JJ, Lai HJ, Sun BW, Lu J, Zeng YY. miR-21 regulates autophagy and apoptosis of ectopic endometrial stromal cells of adenomyosis via PI3K/ AKT/ mTOR pathway. Sci Rep 2025; 15:7639. [PMID: 40038429 PMCID: PMC11880337 DOI: 10.1038/s41598-025-92526-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 02/28/2025] [Indexed: 03/06/2025] Open
Abstract
Adenomyosis (AM) is a common and challenging disease in gynecological clinics, which adversely affects women's physical and mental health. Despite the growing number of studies, the mechanisms associated with the growth of the lesion are poorly understood. Studies show that abnormal proliferation, apoptosis, and migration in ectopic endometrial stromal cells (EESc) of AM may contribute to the development and progression of AM. Understanding the underlying molecular mechanisms can significantly contribute to diagnosing and treating AM. In the present study, EESc was isolated and cultured from the ectopic endometrium of patients with AM. These cells were treated with a PI3K/AKT activator (740 Y-P) and an inhibitor (LY294002), while the expression of microRNA-21 (miR-21) was interfered with. The effects of miR-21 on the apoptosis and autophagy of EESc, as well as the associated mechanisms, were investigated from multiple perspectives. Here, we found that 740 Y-P could significantly promote proliferation, inhibit apoptosis of EESc, and increase the expression of mTOR and p-mTOR proteins in EESc. Moreover, activating miR-21 enhanced the pro-migration effect of 740 Y-P and reversed the pro-apoptotic effect of LY294002, reducing the apoptosis rate and increasing the migration ability of EESc. Our investigation revealed that miR-21 can inhibit apoptosis and autophagy and promote migration of EESc. This effect is likely mediated via the PI3K/AKT/mTOR pathway.
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Affiliation(s)
- Jin-Jin Jia
- Department of Traditional Chinese Medicine, Qinghai Unversity Medical College, Xining, 810016, China
| | - Hui-Jie Lai
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Bo-Wen Sun
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Jie Lu
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Yu-Yan Zeng
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China.
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2
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Silvia Lima RQD, Vasconcelos CFM, Gomes JPA, Bezerra de Menezes EDS, de Oliveira Silva B, Montenegro C, Paiva Júnior SDSL, Pereira MC. miRNA-21, an oncomiR that regulates cell proliferation, migration, invasion and therapy response in lung cancer. Pathol Res Pract 2024; 263:155601. [PMID: 39413459 DOI: 10.1016/j.prp.2024.155601] [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: 03/18/2024] [Revised: 09/10/2024] [Accepted: 09/24/2024] [Indexed: 10/18/2024]
Abstract
Lung cancer is the leading cause of cancer-related death globally, with poor survival rates due mostly to a lack of early detection. The usual diagnostic technique includes a biopsy, which is frequently performed later in the disease's progression. In order to uncover processes that improve illness detection and prognosis, miRNA-21 emerges as a major miRNA identified in a variety of cancer types, including lung cancer. This review compiles insights into the involvement of miRNA-21 within the distinct cellular processes underlying lung cancer. To achieve this, we conducted an extensive literature review, drawing from published in vitro, in vivo and clinical trials studies. Searches were performed in the PubMed, Scielo, CAPES Journal Portal, BVS, INCA, and Clinical Trials.Gov. Only English written articles were selected. As screening criteria, we selected articles that explored the modulation pathways of miRNA-21, along with the proteins and genes implicated in tumorigenesis, metastasis, therapy resistance to established treatments, and their significance in the diagnosis and prognosis of lung cancer. A total of 3294 articles were identified, and 37 papers were selected to compose the review, after analysing selection criteria. Of these, 57 % studies presented in vitro evaluation, 22 % studies showed in vivo analysis, and 12 clinical trials were found. This study elucidates the principal signaling pathways influenced by miRNA-21, which play a pivotal role in lung cancer development. This comprehensive review sheds light on the potential significance of miRNA-21 as a critical mechanism for improving the prognosis of lung cancer patients, facilitating the transition of experimental data into the clinical phase. Therefore, we summarized published articles of miRNA-21 modulated signal pathways in lung cancer.
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Affiliation(s)
| | | | - João Pedro Alves Gomes
- Research Center for Therapeutic Innovation Suely Galdino, Federal University of Pernambuco, Recife, Brazil
| | | | - Barbara de Oliveira Silva
- Research Center for Therapeutic Innovation Suely Galdino, Federal University of Pernambuco, Recife, Brazil
| | - Claudio Montenegro
- Research Center for Therapeutic Innovation Suely Galdino, Federal University of Pernambuco, Recife, Brazil
| | | | - Michelly Cristiny Pereira
- Research Center for Therapeutic Innovation Suely Galdino, Federal University of Pernambuco, Recife, Brazil.
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3
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Chiglintseva D, Clarke DJ, Sen'kova A, Heyman T, Miroshnichenko S, Shan F, Vlassov V, Zenkova M, Patutina O, Bichenkova E. Engineering supramolecular dynamics of self-assembly and turnover of oncogenic microRNAs to drive their synergistic destruction in tumor models. Biomaterials 2024; 309:122604. [PMID: 38733658 DOI: 10.1016/j.biomaterials.2024.122604] [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: 12/10/2023] [Revised: 04/11/2024] [Accepted: 05/05/2024] [Indexed: 05/13/2024]
Abstract
Rationally-engineered functional biomaterials offer the opportunity to interface with complex biology in a predictive, precise, yet dynamic way to reprogram their behaviour and correct shortcomings. Success here may lead to a desired therapeutic effect against life-threatening diseases, such as cancer. Here, we engineered "Crab"-like artificial ribonucleases through coupling of peptide and nucleic acid building blocks, capable of operating alongside and synergistically with intracellular enzymes (RNase H and AGO2) for potent destruction of oncogenic microRNAs. "Crab"-like configuration of two catalytic peptides ("pincers") flanking the recognition oligonucleotide was instrumental here in providing increased catalytic turnover, leading to ≈30-fold decrease in miRNA half-life as compared with that for "single-pincer" conjugates. Dynamic modeling of miRNA cleavage illustrated how such design enabled "Crabs" to drive catalytic turnover through simultaneous attacks at different locations of the RNA-DNA heteroduplex, presumably by producing smaller cleavage products and by providing toeholds for competitive displacement by intact miRNA strands. miRNA cleavage at the 5'-site, spreading further into double-stranded region, likely provided a synergy for RNase H1 through demolition of its loading region, thus facilitating enzyme turnover. Such synergy was critical for sustaining persistent disposal of continually-emerging oncogenic miRNAs. A single exposure to the best structural variant (Crab-p-21) prior to transplantation into mice suppressed their malignant properties and reduced primary tumor volume (by 85 %) in MCF-7 murine xenograft models.
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Affiliation(s)
- Daria Chiglintseva
- Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentiev Avenue, 630090, Novosibirsk, Russia
| | - David J Clarke
- School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
| | - Aleksandra Sen'kova
- Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentiev Avenue, 630090, Novosibirsk, Russia
| | - Thomas Heyman
- School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
| | - Svetlana Miroshnichenko
- Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentiev Avenue, 630090, Novosibirsk, Russia
| | - Fangzhou Shan
- School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
| | - Valentin Vlassov
- Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentiev Avenue, 630090, Novosibirsk, Russia
| | - Marina Zenkova
- Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentiev Avenue, 630090, Novosibirsk, Russia
| | - Olga Patutina
- Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentiev Avenue, 630090, Novosibirsk, Russia.
| | - Elena Bichenkova
- School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
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Wang J, Yang B, Wang Y, Liu S, Ma C, Piao J, Ma S, Yu D, Wu W. CBX2 enhances the progression and TMZ chemoresistance of glioma via EZH2-mediated epigenetic silencing of PTEN expression. Front Pharmacol 2024; 15:1430891. [PMID: 39114365 PMCID: PMC11303140 DOI: 10.3389/fphar.2024.1430891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 07/04/2024] [Indexed: 08/10/2024] Open
Abstract
Chromobox (CBX) 2, a member of the CBX protein family and a crucial component of the polycomb repressive complex (PRC), exerts significant influence on the epigenetic regulation of tumorigenesis, including glioma. However, the precise role of CBX2 in glioma has remained elusive. In our study, we observed a substantial upregulation of CBX2 expression in glioma, which displayed a strong correlation with pathological grade, chemoresistance, and unfavorable prognosis. Through a series of in vivo and in vitro experiments, we established that heightened CBX2 expression facilitated glioma cell proliferation and bolstered resistance to chemotherapy. Conversely, CBX2 knockdown led to a significant inhibition of glioma cell growth and a reduction in chemoresistance. Notably, our investigation uncovered the underlying mechanism by which CBX2 operates, primarily by inhibiting PTEN transcription and activating the AKT/mTOR signalling pathway. Conversely, silencing CBX2 curtailed cell proliferation and attenuated chemoresistance by impeding the activation of the PTEN/AKT/mTOR signalling pathway. Delving deeper into the molecular intricacies, we discovered that CBX2 can recruit EZH2 and modulate the trimethylation of histone H3 lysine 27 (H3K27me3) levels on the PTEN promoter, effectively suppressing PTEN transcription. Our research unveils a comprehensive understanding of how CBX2 impacts the tumorigenesis, progression, chemoresistance, and prognosis of glioma. Furthermore, it presents CBX2 as a promising therapeutic target for drug development and clinical management of glioma.
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Affiliation(s)
- Jian Wang
- Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, China
| | - Bo Yang
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China
| | - Yingzhao Wang
- Department of Neurology, Qianwei Hospital of Jilin Province, Changchun, China
| | - Shuhan Liu
- Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, China
| | - Changkai Ma
- Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, China
| | - Jianmin Piao
- Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, China
| | - Shiqiang Ma
- Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, China
| | - Dehai Yu
- Core Facility, The First Hospital of Jilin University, Changchun, China
| | - Wei Wu
- Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, China
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Cai P, Liu S, Tu Y, Shan T. Toxicity, biodegradation, and nutritional intervention mechanism of zearalenone. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 911:168648. [PMID: 37992844 DOI: 10.1016/j.scitotenv.2023.168648] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 11/14/2023] [Accepted: 11/15/2023] [Indexed: 11/24/2023]
Abstract
Zearalenone (ZEA), a global mycotoxin commonly found in a variety of grain products and animal feed, causes damage to the gastrointestinal tract, immune organs, liver and reproductive system. Many treatments, including physical, chemical and biological methods, have been reported for the degradation of ZEA. Each degradation method has different degradation efficacies and distinct mechanisms. In this article, the global pollution status, hazard and toxicity of ZEA are summarized. We also review the biological detoxification methods and nutritional regulation strategies for alleviating the toxicity of ZEA. Moreover, we discuss the molecular detoxification mechanism of ZEA to help explore more efficient detoxification methods to better reduce the global pollution and hazard of ZEA.
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Affiliation(s)
- Peiran Cai
- College of Animal Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, China; Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou, China
| | - Shiqi Liu
- College of Animal Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, China; Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou, China
| | - Yuang Tu
- College of Animal Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, China; Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou, China
| | - Tizhong Shan
- College of Animal Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, China; Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou, China.
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6
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Sindhoo A, Sipy S, Khan A, Selvaraj G, Alshammari A, Casida ME, Wei DQ. ESOMIR: a curated database of biomarker genes and miRNAs associated with esophageal cancer. Database (Oxford) 2023; 2023:baad063. [PMID: 37815872 PMCID: PMC10563827 DOI: 10.1093/database/baad063] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 07/10/2023] [Accepted: 09/16/2023] [Indexed: 10/12/2023]
Abstract
'Esophageal cancer' (EC) is a highly aggressive and deadly complex disease. It comprises two types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with Barrett's esophagus (BE) being the only known precursor. Recent research has revealed that microRNAs (miRNAs) play a crucial role in the development, prognosis and treatment of EC and are involved in various human diseases. Biological databases have become essential for cancer research as they provide information on genes, proteins, pathways and their interactions. These databases collect, store and manage large amounts of molecular data, which can be used to identify patterns, predict outcomes and generate hypotheses. However, no comprehensive database exists for EC and miRNA relationships. To address this gap, we developed a dynamic database named 'ESOMIR (miRNA in esophageal cancer) (https://esomir.dqweilab-sjtu.com)', which includes information about targeted genes and miRNAs associated with EC. The database uses analysis and prediction methods, including experimentally endorsed miRNA(s) information. ESOMIR is a user-friendly interface that allows easy access to EC-associated data by searching for miRNAs, target genes, sequences, chromosomal positions and associated signaling pathways. The search modules are designed to provide specific data access to users based on their requirements. Additionally, the database provides information about network interactions, signaling pathways and region information of chromosomes associated with the 3'untranslated region (3'UTR) or 5'UTR and exon sites. Users can also access energy levels of specific miRNAs with targeted genes. A fuzzy term search is included in each module to enhance the ease of use for researchers. ESOMIR can be a valuable tool for researchers and clinicians to gain insight into EC, including identifying biomarkers and treatments for this aggressive tumor. Database URL https://esomir.dqweilab-sjtu.com.
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Affiliation(s)
- Asma Sindhoo
- Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Dongchuan Road Minhang District, Shanghai 200240, PR China
| | - Saima Sipy
- Sindh Madressatul Islam University, Karachi, Sindh 74600, Pakistan
| | - Abbas Khan
- Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Dongchuan Road Minhang District, Shanghai 200240, PR China
- State Key Laboratory of Microbial Metabolism, Shanghai–Islamabad–Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai, Minhang 200030, PR China
| | - Gurudeeban Selvaraj
- Centre for Research in Molecular Modelling (CERMM), Department of Chemistry and Biochemistry, Concordia University, Montreal, Quebec H4B 1R6, Canada
| | - Abdulrahman Alshammari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mark Earl Casida
- Laboratoire de Spectrom´etrie, Interactions et Chimie th´eorique (SITh), D´epartement de Chimie Mol´eculaire (DCM, UMR CNRS/UGA 5250), Institut de Chimie Mol´eculaire de Grenoble (ICMG, FR2607), Universit´e Grenoble Alpes (UGA), 301 rue de la Chimie BP 53, Grenoble Cedex F-38041, France
| | - Dong-Qing Wei
- Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Dongchuan Road Minhang District, Shanghai 200240, PR China
- State Key Laboratory of Microbial Metabolism, Shanghai–Islamabad–Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai, Minhang 200030, PR China
- Peng Cheng Laboratory, Phase I Building 8, Xili Street, Montreal, Vanke Cloud City, Nashan District, Shenzhen, Guangdong 518055, PR China
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Bilan F, Amini M, Doustvandi MA, Tohidast M, Baghbanzadeh A, Hosseini SS, Mokhtarzadeh A, Baradaran B. Simultaneous suppression of miR-21 and restoration of miR-145 in gastric cancer cells; a promising strategy for inhibition of cell proliferation and migration. BIOIMPACTS : BI 2023; 14:27764. [PMID: 38505672 PMCID: PMC10945301 DOI: 10.34172/bi.2023.27764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 06/13/2023] [Accepted: 06/25/2023] [Indexed: 03/21/2024]
Abstract
Introduction Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. microRNAs are a group of regulatory non-coding RNAs that are involved in GC progression. miR-145 as a tumor suppressor and miR-21 as an oncomiR were shown to be dysregulated in many cancers including GC. This research aimed to enhance the expression of miR-145 while reducing the expression of miR-21 and examine their impact on the proliferation, apoptosis, and migration of GC cells. Methods KATO III cells with high expression levels of miR-21-5p and low expression of miR-145-5p were selected. These cells were then transfected with either miR-145-5p mimics or anti-miR-21-5p, alone or in combination. Afterward, the cell survival rate was determined using the MTT assay, while apoptosis induction was investigated through V-FITC/PI and DAPI staining. Additionally, cell migration was examined using the wound healing assay, and cell cycle progression was analyzed through flow cytometry. Furthermore, gene expression levels were quantified utilizing the qRT-PCR technique. Results The study's findings indicated that the co-replacement of miR-145-5p and anti-miR-21-5p led to a decrease in cell viability and the induction of apoptosis in GC cells. This was achieved via modulating the expression of Bax and Bcl-2, major cell survival regulators. Additionally, the combination therapy significantly increased sub-G1 cell cycle arrest and reduced cell migration by downregulating MMP-9 expression as an epithelial-mesenchymal transition marker. This study provides evidence for the therapeutic possibility of the combination of miR-145-5p and anti-miR-21-5p and also suggests that they could inhibit cell proliferation by modulating the PTEN/AKT1 signaling pathway. Conclusion Our research revealed that utilizing miR-145-5p and anti-miR-21-5p together could be a promising therapeutic approach for treating GC.
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Affiliation(s)
- Farzaneh Bilan
- Department of Biological Science, Faculty of Basic Science, Higher Education Institute of Rab-Rashid, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Maryam Tohidast
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Baghbanzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Doghish AS, El-Husseiny AA, Abdelmaksoud NM, El-Mahdy HA, Elsakka EGE, Abdel Mageed SS, Mahmoud AMA, Raouf AA, Elballal MS, El-Dakroury WA, AbdelRazek MMM, Noshy M, El-Husseiny HM, Abulsoud AI. The interplay of signaling pathways and miRNAs in the pathogenesis and targeted therapy of esophageal cancer. Pathol Res Pract 2023; 246:154529. [PMID: 37196470 DOI: 10.1016/j.prp.2023.154529] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/19/2023]
Abstract
Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-β signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Ahmed A El-Husseiny
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Cairo, Egypt
| | - Nourhan M Abdelmaksoud
- Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Abdulla M A Mahmoud
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Amr Raouf
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohamed M M AbdelRazek
- Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mina Noshy
- Clinical Pharmacy Department, Faculty of Pharmacy, King Salman International University (KSIU), SouthSinai, Ras Sudr 46612, Egypt
| | - Hussein M El-Husseiny
- Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan; Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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9
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Farasati Far B, Vakili K, Fathi M, Yaghoobpoor S, Bhia M, Naimi-Jamal MR. The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: A review. Life Sci 2023; 316:121340. [PMID: 36586571 DOI: 10.1016/j.lfs.2022.121340] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/16/2022] [Accepted: 12/26/2022] [Indexed: 12/29/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of several target genes. miRNAs play a significant role in cancer biology, as they can downregulate their corresponding target genes by impeding the translation of mRNA (at the mRNA level) as well as degrading mRNAs by binding to the 3'-untranslated (UTR) regions (at the protein level). miRNAs may be employed as cancer biomarkers. Therefore, miRNAs are widely investigated for early detection of cancers which can lead to improved survival rates and quality of life. This is particularly important in the case of gastrointestinal cancers, where early detection of the disease could substantially impact patients' survival. MicroRNA-21 (miR-21 or miRNA-21) is one of the most frequently researched miRNAs, where it is involved in the pathophysiology of cancer and the downregulation of several tumor suppressor genes. In gastrointestinal cancers, miR-21 regulates phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), mothers against decapentaplegic homolog 7 (SMAD7), phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), matrix metalloproteinases (MMPs), β-catenin, tropomyosin 1, maspin, and ras homolog gene family member B (RHOB). In this review, we investigate the functions of miR-21 in pathogenesis and its applications as a diagnostic and prognostic cancer biomarker in four different gastrointestinal cancers, including colorectal cancer (CRC), pancreatic cancer (PC), gastric cancer (GC), and esophageal cancer (EC).
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Affiliation(s)
- Bahareh Farasati Far
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
| | - Kimia Vakili
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Fathi
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shirin Yaghoobpoor
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammed Bhia
- Student Research Committee, Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Reza Naimi-Jamal
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.
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Musi A, Bongiovanni L. Extracellular Vesicles in Cancer Drug Resistance: Implications on Melanoma Therapy. Cancers (Basel) 2023; 15:1074. [PMID: 36831417 PMCID: PMC9954626 DOI: 10.3390/cancers15041074] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/29/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Extracellular vesicles (EVs) are involved in the pathogenesis of neoplastic diseases. Their role in mediating drug resistance has been widely described in several types of cancers, including melanoma. EVs can mediate drug resistance through several different mechanisms, such as drug-sequestration, transfer of pro-survival proteins and RNA, induction of cancer stem cell-like features and interaction with cells of the tumor microenvironment and immune-system. Melanoma is a highly immunogenic tumor originating from the malignant transformation of melanocytes. Several therapeutic strategies currently used in the treatment of melanoma and the combination of BRAF and MEK-inhibitors, as well as immune check-point inhibitors (ICI), have consistently improved the overall survival time of melanoma patients. However, the development of resistance is one of the biggest problems leading to a poor clinical outcome, and EVs can contribute to this. EVs isolated from melanoma cells can contain "sequestered" chemotherapeutic drugs in order to eliminate them, or bioactive molecules (such as miRNA or proteins) that have been proven to play a crucial role in the transmission of resistance to sensitive neoplastic cells. This leads to the hypothesis that EVs could be considered as resistance-mediators in sensitive melanoma cells. These findings are a pivotal starting point for further investigations to better understand EVs' role in drug resistance mechanisms and how to target them. The purpose of this review is to summarize knowledge about EVs in order to develop a deeper understanding of their underlying mechanisms. This could lead to the development of new therapeutic strategies able to bypass EV-mediated drug-resistance in melanoma, such as by the use of combination therapy, including EV release inhibitors.
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Affiliation(s)
- Alice Musi
- Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy
| | - Laura Bongiovanni
- Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy
- Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584CT Utrecht, The Netherlands
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11
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Cariello M, Squilla A, Piacente M, Venutolo G, Fasano A. Drug Resistance: The Role of Exosomal miRNA in the Microenvironment of Hematopoietic Tumors. Molecules 2022; 28:molecules28010116. [PMID: 36615316 PMCID: PMC9821808 DOI: 10.3390/molecules28010116] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/07/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
Extracellular vesicles (EVs), including exosomes, have an important role thanks to their ability to communicate and exchange information between tumor cells and the tumor microenvironment (TME), and have also been associated with communicating anti-cancer drug resistance (DR). The increase in proliferation of cancer cells alters oxygen levels, which causes hypoxia and results in a release of exosomes by the cancer cells. In this review, the results of studies examining the role of exosomal miRNA in DR, and their mechanism, are discussed in detail in hematological tumors: leukemia, lymphoma, and multiple myeloma. In conclusion, we underline the exosome's function as a possible drug delivery vehicle by understanding its cargo. Engineered exosomes can be used to be more specific for personalized therapy.
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Affiliation(s)
- Mariaconcetta Cariello
- European Biomedical Research Institute of Salerno (EBRIS), Via S. de Renzi, 84125 Salerno, Italy
| | - Angela Squilla
- European Biomedical Research Institute of Salerno (EBRIS), Via S. de Renzi, 84125 Salerno, Italy
| | - Martina Piacente
- European Biomedical Research Institute of Salerno (EBRIS), Via S. de Renzi, 84125 Salerno, Italy
| | - Giorgia Venutolo
- European Biomedical Research Institute of Salerno (EBRIS), Via S. de Renzi, 84125 Salerno, Italy
| | - Alessio Fasano
- European Biomedical Research Institute of Salerno (EBRIS), Via S. de Renzi, 84125 Salerno, Italy
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA 02114, USA
- Correspondence: ; Tel.: +1-617-724-4604
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12
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SIX3 function in cancer: progression and comprehensive analysis. Cancer Gene Ther 2022; 29:1542-1549. [PMID: 35764712 DOI: 10.1038/s41417-022-00488-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 05/02/2022] [Accepted: 05/27/2022] [Indexed: 02/04/2023]
Abstract
The homeobox gene family encodes transcription factors that are essential for cell growth, proliferation, and differentiation, and its dysfunction is linked to tumor initiation and progression. Sine oculis homeobox (SIX) belongs to the homeobox gene family, with SIX3 being a core member. Recent studies indicate that SXI3 functions as a cancer suppressor or promoter, which is mainly dependent on SIX3's influence on the signal pathways that promote or inhibit cancer in cells. The low expression of SIX3 in most malignant tumors was confirmed by detailed studies, which could promote the cell cycle, proliferation, migration, and angiogenesis. The recovery or upregulation of SIX3 expression to suppress cancer is closely related to the direct or indirect inhibition of the Wnt pathway. However, in some malignancies, such as esophageal cancer and gastric cancer, SIX3 is a tumor-promoting factor, and repressing SIX3 improves patients' prognosis. This review introduces the research progress of SIX3 in tumors and gives a comprehensive analysis, intending to explain why SIX3 plays different roles in different cancers and provide new cancer therapy strategies.
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13
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Dhuri K, Pradeep SP, Shi J, Anastasiadou E, Slack FJ, Gupta A, Zhong XB, Bahal R. Simultaneous Targeting of Multiple oncomiRs with Phosphorothioate or PNA-Based Anti-miRs in Lymphoma Cell Lines. Pharm Res 2022; 39:2709-2720. [PMID: 36071352 PMCID: PMC9879158 DOI: 10.1007/s11095-022-03383-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 08/27/2022] [Indexed: 01/29/2023]
Abstract
PURPOSE MicroRNAs (miRNAs) are short (~ 22 nts) RNAs that regulate gene expression via binding to mRNA. MiRNAs promoting cancer are known as oncomiRs. Targeting oncomiRs is an emerging area of cancer therapy. OncomiR-21 and oncomiR-155 are highly upregulated in lymphoma cells, which are dependent on these oncomiRs for survival. Targeting specific miRNAs and determining their effect on cancer cell progression and metastasis have been the focus of various studies. Inhibiting a single miRNA can have a limited effect, as there may be other overexpressed miRNAs present that may promote tumor proliferation. Herein, we target miR-21 and miR-155 simultaneously using nanoparticles delivered two different classes of antimiRs: phosphorothioates (PS) and peptide nucleic acids (PNAs) and compared their efficacy in lymphoma cell lines. METHODS Poly-Lactic-co-Glycolic acid (PLGA) nanoparticles (NPs) containing PS and PNA-based antimiR-21 and -155 were formulated, and comprehensive NP characterizations: morphology (scanning electron microscopy), size (differential light scattering), and surface charge (zeta potential) were performed. Cellular uptake analysis was performed using a confocal microscope and flow cytometry analysis. The oncomiR knockdown and the effect on downstream targets were confirmed by gene expression (real time-polymerase chain reaction) assay. RESULTS We demonstrated that simultaneous targeting with NP delivered PS and PNA-based antimiRs resulted in significant knockdown of miR-21 and miR-155, as well as their downstream target genes followed by reduced cell viability ex vivo. CONCLUSIONS This project demonstrated that targeting miRNA-155 and miR-21 simultaneously using nanotechnology and a diverse class of antisense oligomers can be used as an effective approach for lymphoma therapy.
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Affiliation(s)
- Karishma Dhuri
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Sai Pallavi Pradeep
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Jason Shi
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Eleni Anastasiadou
- HMS Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA
| | - Frank J Slack
- HMS Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA
| | - Anisha Gupta
- School of Pharmacy, University of Saint Joseph, West Hartford, CT, 06117, USA
| | - Xiao-Bo Zhong
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Raman Bahal
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA.
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14
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Ghafouri-Fard S, Noie Alamdari A, Noee Alamdari Y, Abak A, Hussen BM, Taheri M, Jamali E. Role of PI3K/AKT pathway in squamous cell carcinoma with an especial focus on head and neck cancers. Cancer Cell Int 2022; 22:254. [PMID: 35964082 PMCID: PMC9375325 DOI: 10.1186/s12935-022-02676-x] [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: 02/05/2022] [Accepted: 08/05/2022] [Indexed: 11/21/2022] Open
Abstract
PI3K/AKT pathway is an important pathway in the carcinogenesis since it has central impacts in the regulation of metabolic pathways, cell proliferation and survival, gene expression and protein synthesis. This pathway has been reported to be dysregulated in several types of cancers. In the current review, we summarize the role of this signaling pathway in squamous cell carcinomas (SCCs) originated from different parts of body cervix, oral cavity, head and neck and skin. The data presented in the current review shows the impact of dysregulation of PI3K/AKT pathway in survival of patients with SCC. Moreover, targeted therapies against this pathway have been found to be effective in reduction of tumor burden both in animal models and clinical settings. Finally, a number of molecules that regulate PI3K/AKT pathway can be used as diagnostic markers for different types of SCCs.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Noie Alamdari
- Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Atefe Abak
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil, Iraq.,Center of Research and Strategic Studies, Lebanese French University, Kurdistan Region, Erbil, Iraq
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany. .,Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Elena Jamali
- Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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15
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Zhou W, Zhu H, Xu Y, Gu L, Wu W, Zhang Y, Huang X, Jiang Y. miR-498/DNMT3b Axis Mediates Resistance to Radiotherapy in Esophageal Cancer Cells. Cancer Biother Radiopharm 2022; 37:287-299. [PMID: 33885332 DOI: 10.1089/cbr.2020.4227] [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] [Indexed: 11/13/2022] Open
Abstract
Objective: To explore the role of miR-498 in the radiotherapy resistance of esophageal cancer (EC) and its underlying mechanism. Methods: In vivo models of EC tissues with radioresistance or radiosensitivity were isolated from 72 EC patients who received radiotherapy. In vitro models were established after irradiation of KYSE30 cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were employed to measure the expression levels of miR-498 and DNMT3b in EC cells sensitive or resistant to irradiation. Then, protein expression of DNMT3b was verified by immunohistochemistry. The cell viability, colony formation rate, and cell apoptotic rate of EC were correspondingly assessed by CCK-8, colony formation assay, and Annexin V/PI (propidium iodide) double staining. Western blot was utilized to perform the expression levels of PI3K, p-PI3K, AKT, and p-AKT in EC cell lines after irradiation. Results: Highly expressed DNMT3b and lowly expressed miR-498 were found in EC tissues. EC tissues with radiosensitivity had higher miR-498 level and lower DNMT3b expression than EC tissues with radioresistance. Overexpression of miR-498 or knockdown of DNMT3b enhanced the radiosensitivity of EC cells. DNMT3b was a target gene of miR-498. DNMT3b diminished the radiosensitization of miR-498 in EC cells. Conclusions: MiR-498 enhances the sensitivity of EC cells to radiation by DNMT3b inhibition, and exerts biological functions by inactivating the PI3K/AKT signaling pathway.
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Affiliation(s)
- Weihe Zhou
- Department of Cardiothoracic Surgery and the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
| | - Haoqi Zhu
- Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
| | - Yuan Xu
- Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
| | - Lizhong Gu
- Department of Cardiothoracic Surgery and the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
| | - Weijia Wu
- Department of Cardiothoracic Surgery and the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
| | - Yuefeng Zhang
- Department of Cardiothoracic Surgery and the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
| | - Xianping Huang
- Department of Cardiothoracic Surgery and the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
| | - Yi Jiang
- Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
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16
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Qiu R, Wang W, Li J, Wang Y. Roles of PTEN inactivation and PD-1/PD-L1 activation in esophageal squamous cell carcinoma. Mol Biol Rep 2022; 49:6633-6645. [PMID: 35301651 DOI: 10.1007/s11033-022-07246-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 02/04/2022] [Accepted: 02/08/2022] [Indexed: 02/07/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China and developing countries. The purpose of this review is to summarize the roles of inactivation of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), and activation of the programmed cell death protein 1 (PD-1) upon binding to its ligand (PD-L1) in the promotion of ESCC. Studies of ESCC performed in vitro and in vivo indicated that PTEN and PD-L1 function in the regulation of cell proliferation, invasion, and migration; the epithelial-mesenchymal transition; resistance to chemotherapy and radiotherapy; and the PI3K/AKT signaling pathway. Certain genetic variants of PTEN are related to susceptibility to ESCC, and PTEN and PD-L1 also function in ESCC progression and affect the prognosis of patients with ESCC. There is also evidence that the expression of PD-L1 and PTEN are associated with the progression of certain other cancers. Future studies should further examine the relationship of PD-L1 and PTEN and their possible interactions in ESCC.
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Affiliation(s)
- Rong Qiu
- Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, No. 12 Jian Kang Road, Shijiazhuang, Hebei Province, P. R. China
| | - Wenxi Wang
- Department of Oncology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan Province, China
| | - Juan Li
- Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, No. 12 Jian Kang Road, Shijiazhuang, Hebei Province, P. R. China
| | - Yuxiang Wang
- Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, No. 12 Jian Kang Road, Shijiazhuang, Hebei Province, P. R. China.
- , No.12, Jiankang Road, 050011, Shijiazhuang, Hebei Province, China.
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17
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Cao P, Nie G, Luo J, Hu R, Li G, Hu G, Zhang C. Cadmium and molybdenum co-induce pyroptosis and apoptosis by PTEN/PI3K/AKT axis in the liver of ducks. Food Funct 2022; 13:2142-2154. [DOI: 10.1039/d1fo02855c] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Cadmium (Cd) and excessive molybdenum (Mo) have adverse impacts on animals. However, the hepatotoxicity co-induced by Cd and Mo in ducks has not been fully elucidated. In order to explore...
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18
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Li LZ, Wu ZZ, Lv Z. The Clinical Significance of miR-21 in Guiding Chemotherapy for Patients with Osteosarcoma. Pharmgenomics Pers Med 2021; 14:1247-1261. [PMID: 34616172 PMCID: PMC8488037 DOI: 10.2147/pgpm.s321637] [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: 05/24/2021] [Accepted: 08/16/2021] [Indexed: 11/23/2022] Open
Abstract
Objective The present study aims to explore the correlation between osteosarcoma (OS) chemosensitivity and the expression levels of serum and tumor tissue micro-ribonucleic acid-21 (miR-21). Methods The relevant miR-21 expression levels in 30 patients with OS were detected, and the gender, age, tumor location, pathological type, Enneking stage, and miR-21 expression changes before and after chemotherapy were retrospectively analyzed. Results Serum and tumor tissue miR21 expression levels were significantly higher in patients with OS than in control subjects; the serum miR-21 expressions before and after chemotherapy were not related to patient age and gender. The effective chemotherapy group showed significant differences in miR-21 expression levels before and after chemotherapy. Conclusion Serum and tumor tissue miR-21 expression levels in patients with OS are closely related to the effects of chemotherapy, making miR-21 a potential biomarker and therapeutic target for the diagnosis and evaluation of chemotherapy effects on patients with OS.
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Affiliation(s)
- Li-Zhi Li
- Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China
| | - Zhuang-Zhuang Wu
- Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China
| | - Zhi Lv
- Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China
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Xu J, Pan HW, Wang XQ, Chen KP. Status of diagnosis and treatment of esophageal cancer and non-coding RNA correlation research: a narrative review. Transl Cancer Res 2021; 10:4532-4552. [PMID: 35116309 PMCID: PMC8798506 DOI: 10.21037/tcr-21-687] [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: 04/21/2021] [Accepted: 08/20/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To describe and discuss the progression of the non-coding RNA as biomarkers in early esophageal cancer. BACKGROUND Esophageal cancer without obvious symptoms during early stages is one of the most common cancers, the current clinical treatments offer possibilities of a cure, but the survival rates and the prognoses remain poor, it is a serious threat to human life and health. Most patients are usually diagnosed during terminal stages due to low sensitivity of esophageal cancer's early detection techniques. With the development of molecular biology, an increasing number of non-coding RNAs are found to be associated with the occurrence, development, and prognosis of esophageal cancer. Some of these have begun to be used in clinics and laboratories for diagnosis, treatment, and prognosis, with the goal of reducing mortality. METHODS The information for this paper was collected from a variety of sources, including a search of the keynote's references, a search for texts in college libraries, and discussions with experts in the field of esophageal cancer clinical treatment. CONCLUSIONS Non-coding RNA does play a regulatory role in the development of esophageal cancer, which can predict the occurrence or prognosis of tumors, and become a new class of tumor markers and therapeutic targets in clinical applications. In this review, we survey the recent developments in the incidence, diagnosis, and treatment of esophageal cancer, especially with new research progresses on non-coding RNA biomarkers in detail, and discuss its potential clinical applications.
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Affiliation(s)
- Jia Xu
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Hui-Wen Pan
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Xue-Qi Wang
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Ke-Ping Chen
- School of Life Sciences, Jiangsu University, Zhenjiang, China
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20
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Nguyen TT, Ung TT, Li S, Sah DK, Park SY, Lian S, Jung YD. Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells. Int J Mol Sci 2021; 22:10209. [PMID: 34638550 PMCID: PMC8508661 DOI: 10.3390/ijms221910209] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/15/2021] [Accepted: 09/17/2021] [Indexed: 11/19/2022] Open
Abstract
Micro-RNA-21 (miR-21) is a vital regulator of colorectal cancer (CRC) progression and has emerged as a potential therapeutic target in CRC treatment. Our study using real-time PCR assay found that a secondary bile acid, lithocholic acid (LCA), stimulated the expression of miR21 in the CRC cell lines. Promoter activity assay showed that LCA strongly stimulated miR21 promoter activity in HCT116 cells in a time- and dose-dependent manner. Studies of chemical inhibitors and miR21 promoter mutants indicated that Erk1/2 signaling, AP-1 transcription factor, and STAT3 are major signals involved in the mechanism of LCA-induced miR21 in HCT116 cells. The elevation of miR21 expression was upstream of the phosphatase and tensin homolog (PTEN) inhibition, and CRC cell proliferation enhancement that was shown to be possibly mediated by PI3K/AKT signaling activation. This study is the first to report that LCA affects miR21 expression in CRC cells, providing us with a better understanding of the cancer-promoting mechanism of bile acids that have been described as the very first promoters of CRC progression.
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Affiliation(s)
- Thinh-Thi Nguyen
- Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea; (T.-T.N.); (T.-T.U.); (S.L.); (D.K.S.); (S.-Y.P.)
- Nanogen Pharmaceutical Biotechnology Joint Stock Company, Ho Chi Minh City 71207, Vietnam
| | - Thuan-Trong Ung
- Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea; (T.-T.N.); (T.-T.U.); (S.L.); (D.K.S.); (S.-Y.P.)
- Nanogen Pharmaceutical Biotechnology Joint Stock Company, Ho Chi Minh City 71207, Vietnam
| | - Shinan Li
- Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea; (T.-T.N.); (T.-T.U.); (S.L.); (D.K.S.); (S.-Y.P.)
| | - Dhiraj Kumar Sah
- Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea; (T.-T.N.); (T.-T.U.); (S.L.); (D.K.S.); (S.-Y.P.)
| | - Sun-Young Park
- Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea; (T.-T.N.); (T.-T.U.); (S.L.); (D.K.S.); (S.-Y.P.)
| | - Sen Lian
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Young-Do Jung
- Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea; (T.-T.N.); (T.-T.U.); (S.L.); (D.K.S.); (S.-Y.P.)
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Yiming Z, Zhaoyi L, Jing L, Jinliang W, Zhiqiang S, Guangliang S, Shu L. Cadmium induces the thymus apoptosis of pigs through ROS-dependent PTEN/PI3K/AKT signaling pathway. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:39982-39992. [PMID: 33765263 DOI: 10.1007/s11356-021-13517-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 03/15/2021] [Indexed: 06/12/2023]
Abstract
Cadmium (Cd) is a transition metal that is toxic to living organisms in the environment and endangers living organisms. To explore whether Cd induces apoptosis in pig thymus and its possible mechanism, the role Cd induction of the PTEN/PI3K/Akt pathway in apoptosis of thymus cells was studied in pigs. We found that Cd exposure (the feed is treated with Cd) significantly increased Cd accumulation in the thymus of pigs. The TUNEL assay confirmed the typical apoptotic characteristics of thymus in Cd group. Moreover, in the Cd group, the activities of antioxidant indices decreased significantly, while the levels of oxidative stress indexes increased significantly, and the mRNA levels of GSH, CAT, Gpx1, GST, SOD1, and SOD2 decreased obviously. Moreover, the mRNA and protein levels of PTEN/PI3K/AKT and apoptosis-related genes were detected by qPCR and western blotting. The results show that the expressions of PI3K and AKT decreased, while the expression of PTEN increased, indicating that pathway activated. With the PTEN/PI3K/AKT pathway regulating, Bcl-2 expression decreased. Conversely, the mRNA and protein expression of apoptosis-related genes were up-regulated. In conclusion, accumulation of Cd in the pigs caused oxidative damage to immune tissues. In addition, Cd-induced oxidative stress activates the PTEN/PI3K/AKT pathway, inducing apoptosis in the thymus of pigs.
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Affiliation(s)
- Zhang Yiming
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Liu Zhaoyi
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Lan Jing
- Quality and Safety Institute of Agricultural Products, Heilongjiang Academy of Agricultural Sciences, Harbin, 150000, China
| | - Wang Jinliang
- Shandong Binzhou Anim Sci & Vet Med Acad, Binzhou, 256600, People's Republic of China
| | - Shen Zhiqiang
- Shandong Binzhou Anim Sci & Vet Med Acad, Binzhou, 256600, People's Republic of China
| | - Shi Guangliang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
| | - Li Shu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
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22
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Yao W, Jia X, Xu L, Li S, Wei L. MicroRNA-2053 involves in the progression of esophageal cancer by targeting KIF3C. Cell Cycle 2021; 20:1163-1172. [PMID: 34057012 DOI: 10.1080/15384101.2021.1929675] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
This study aimed to explore the role of micorRNA-2053 in esophageal cancer development. The expression level of miR-2053 in esophageal cancer cell lines was detected. After cell transfection, the effects of miR-2053 overexpression on proliferation, apoptosis, migration and invasion of esophageal cancer cells were determined. Moreover, the potential molecular mechanism was explored by measuring the epithelial-mesenchymal transition (EMT) and apoptosis-related proteins. Luciferase reporter assay was conducted to investigate the target gene of miR-2053. The protein expressions of PI3K/AKT pathway associated factors were detected after overexpression of miR-2053 or administration with the pathway inhibitor LY294002. The miR-2053 was downregulated in esophageal cancer cell lines. Overexpression of miR-2053 inhibited cell proliferation, migration and invasion while promoted apoptosis. Molecular mechanism elucidated that miR-2053 could reduce EMT and elevate the expression of pro-apoptotic proteins. Further study found that overexpressed miR-2053 could negatively regulate KIF3C and involve in PI3K/AKT signaling pathway. Our study demonstrated the downregulation of miR-2053 in esophageal cancer. Downregulation of miR-2053 involved in the proliferation, apoptosis, migration and invasion of esophageal cancer cells through upregulating KIF3C expression and activating the PI3K/AKT signaling pathway. miR-2053 may have the potential in clinical treatment of esophageal cancer.
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Affiliation(s)
- Wenjian Yao
- Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
| | - Xiangbo Jia
- Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
| | - Lei Xu
- Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
| | - Saisai Li
- Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
| | - Li Wei
- Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
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Nguyen HT, Kacimi SEO, Nguyen TL, Suman KH, Lemus-Martin R, Saleem H, Do DN. MiR-21 in the Cancers of the Digestive System and Its Potential Role as a Diagnostic, Predictive, and Therapeutic Biomarker. BIOLOGY 2021; 10:biology10050417. [PMID: 34066762 PMCID: PMC8151274 DOI: 10.3390/biology10050417] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/27/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs. They can regulate the expression of their target genes, and thus, their dysregulation significantly contributes to the development of cancer. Growing evidence suggests that miRNAs could be used as cancer biomarkers. As an oncogenic miRNA, the roles of miR-21 as a diagnostic and prognostic biomarker, and its therapeutic applications have been extensively studied. In this review, the roles of miR-21 are first demonstrated via its different molecular networks. Then, a comprehensive review on the potential targets and the current applications as a diagnostic and prognostic cancer biomarker and the therapeutic roles of miR-21 in six different cancers in the digestive system is provided. Lastly, a brief discussion on the challenges for the use of miR-21 as a therapeutic tool for these cancers is added.
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Affiliation(s)
- Ha Thi Nguyen
- Institute of Research and Development, Duy Tan University, Danang 550000, Vietnam;
- Faculty of Medicine, Duy Tan University, Danang 550000, Vietnam
| | | | - Truc Ly Nguyen
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea;
| | - Kamrul Hassan Suman
- Department of Fisheries Biology & Aquatic Environment, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh;
| | | | - Humaira Saleem
- Jamil–ur–Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;
| | - Duy Ngoc Do
- Department of Animal Science and Aquaculture, Dalhousie University, Truro, NS B2N5E3, Canada
- Correspondence: ; Tel.: +1-819-571-5310
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Zhao Y, Wang T, Li P, Chen J, Nepovimova E, Long M, Wu W, Kuca K. Bacillus amyloliquefaciens B10 can alleviate aflatoxin B1-induced kidney oxidative stress and apoptosis in mice. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2021; 218:112286. [PMID: 33933810 DOI: 10.1016/j.ecoenv.2021.112286] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 04/10/2021] [Accepted: 04/22/2021] [Indexed: 06/12/2023]
Abstract
Aflatoxin B1(AFB1) widely exists in food and feed, which seriously endangers human and animal health. How to detoxify AFB1 is a research hotspot at present. This study attempts to use the Bacillus amyloliquefaciens B10, one of probiotics strain as the research object to ascertain whether it can alleviate the kidney injury induced by AFB1 in mice and its mechanism. Fifty-six mice were divided into four groups (control, AFB1, AFB1 + B10, and B10). The mice that received intragastric administration for 28 days were euthanised, and serum was collected for biochemical index detection with fresh kidney tissue taken for HE staining, TUNEL detection, and protein expression detection. Our results showed that the biochemical indices changed, significant pathological changes appeared, the number of apoptotic cells increased in the kidney tissue of the AFB1 group mice; the protein expressions of Nrf2, HO-1,AKT, P-AKT, and Bcl-2 in the AFB1 group were significantly decreased; the protein expressions of Keap-1, PTEN, Bax, Caspase-9, and Caspase-3 were significantly increased. After B. amyloliquefaciens B10 co-treatment, compared with the AFB1 group, the biochemical indices, pathological changes, and protein expressions were significantly reversed. The results indicated that B. amyloliquefaciens B10 can alleviate AFB1-induced kidney injury in mice.
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Affiliation(s)
- Yeqi Zhao
- College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Tiancheng Wang
- College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Peng Li
- College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Jia Chen
- College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic
| | - Miao Long
- College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China.
| | - Wenda Wu
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic.
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic.
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Maleki S, Jabalee J, Garnis C. The Role of Extracellular Vesicles in Mediating Resistance to Anticancer Therapies. Int J Mol Sci 2021; 22:4166. [PMID: 33920605 PMCID: PMC8073860 DOI: 10.3390/ijms22084166] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/10/2021] [Accepted: 04/12/2021] [Indexed: 12/22/2022] Open
Abstract
Although advances in targeted therapies have driven great progress in cancer treatment and outcomes, drug resistance remains a major obstacle to improving patient survival. Several mechanisms are involved in developing resistance to both conventional chemotherapy and molecularly targeted therapies, including drug efflux, secondary mutations, compensatory genetic alterations occurring upstream or downstream of a drug target, oncogenic bypass, drug activation and inactivation, and DNA damage repair. Extracellular vesicles (EVs) are membrane-bound lipid bilayer vesicles that are involved in cell-cell communication and regulating biological processes. EVs derived from cancer cells play critical roles in tumor progression, metastasis, and drug resistance by delivering protein and genetic material to cells of the tumor microenvironment. Understanding the biochemical and genetic mechanisms underlying drug resistance will aid in the development of new therapeutic strategies. Herein, we review the role of EVs as mediators of drug resistance in the context of cancer.
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Affiliation(s)
- Saeideh Maleki
- Postgraduate Program in Interdisciplinary Oncology, Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada; (S.M.); (J.J.)
| | - James Jabalee
- Postgraduate Program in Interdisciplinary Oncology, Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada; (S.M.); (J.J.)
| | - Cathie Garnis
- Postgraduate Program in Interdisciplinary Oncology, Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada; (S.M.); (J.J.)
- Department of Surgery, University of British Columbia, Vancouver, BC V5Z 1M9, Canada
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Wang D, Yan S, Wang L, Li Y, Qiao B. circSLC8A1 Acts as a Tumor Suppressor in Prostate Cancer via Sponging miR-21. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6614591. [PMID: 33869627 PMCID: PMC8035017 DOI: 10.1155/2021/6614591] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/12/2021] [Accepted: 03/17/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND There is more and more evidence showed that circRNAs played essentially role in the regulation of various biological processes. The role of circSLC8A1 in prostate cancer (PCa) is yet little known. METHODS The CircSLC8A1 expression in human prostate cancer was measured by qRT-PCR. The interplay between the specific circRNA, miRNA, and mRNA was investigated by RT-PCR and luciferase reporter assay. Through transient transfection of siRNA, the impacts of circSLC8A1 on PCa were discussed. Cell cycle evaluation, transwell assay, and CCK-8 assay were employed to determine its biological influences. RESULTS In this study, our data revealed that circSLC8A1 was downregulated in PCa tissues and cells. The reduction of circSLC8A1 resulted in the inhibition of cell proliferation and migration. In mechanism, circSLC8A1 exhibited a direct interaction with miR-21 and displayed as a miRNA sponge to inhibit PCa progression. The functional analysis revealed that the circSLC8A1/miR-21 axis may regulate the cell proliferation, angiogenesis, cell migration, epithelial to mesenchymal transition, MAPK signaling pathway, and chemokine signaling pathway. CONCLUSIONS CircSLC8A1 functioned as an inhibitor of neoplasm via modulating the miR-21 and might serve as a prospective target for the treatment of PCa.
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Affiliation(s)
- Daoyuan Wang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Urology, 989th Hospital of the Joint Logistic Support Force, Luoyang, China
| | - Shuxian Yan
- Department of Urology, 989th Hospital of the Joint Logistic Support Force, Luoyang, China
| | - Lihui Wang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yunlong Li
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Baoping Qiao
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences. Molecules 2021; 26:molecules26061732. [PMID: 33808835 PMCID: PMC8003597 DOI: 10.3390/molecules26061732] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 03/18/2021] [Accepted: 03/19/2021] [Indexed: 11/17/2022] Open
Abstract
RNA-targeting therapeutics require highly efficient sequence-specific devices capable of RNA irreversible degradation in vivo. The most developed methods of sequence-specific RNA cleavage, such as siRNA or antisense oligonucleotides (ASO), are currently based on recruitment of either intracellular multi-protein complexes or enzymes, leaving alternative approaches (e.g., ribozymes and DNAzymes) far behind. Recently, site-selective artificial ribonucleases combining the oligonucleotide recognition motifs (or their structural analogues) and catalytically active groups in a single molecular scaffold have been proven to be a great competitor to siRNA and ASO. Using the most efficient catalytic groups, utilising both metal ion-dependent (Cu(II)-2,9-dimethylphenanthroline) and metal ion-free (Tris(2-aminobenzimidazole)) on the one hand and PNA as an RNA recognising oligonucleotide on the other, allowed site-selective artificial RNases to be created with half-lives of 0.5-1 h. Artificial RNases based on the catalytic peptide [(ArgLeu)2Gly]2 were able to take progress a step further by demonstrating an ability to cleave miRNA-21 in tumour cells and provide a significant reduction of tumour growth in mice.
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Time series expression pattern of key genes reveals the molecular process of esophageal cancer. Biosci Rep 2021; 40:222161. [PMID: 32068233 PMCID: PMC7048673 DOI: 10.1042/bsr20191985] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 11/24/2019] [Accepted: 12/16/2019] [Indexed: 12/18/2022] Open
Abstract
Background: Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world. Although a series of studies on esophageal cancer have been reported, the molecular pathogenesis of the disease is still elusive. Aim: To investigate the molecular process of esophageal cancer comprehensively and deeply. Methods: Differential expression analysis was performed to identify differentially expressed genes (DEGs) in different stages of esophageal cancer. Then exacting gene interaction modules and hub genes were identified in module interaction network. Further, though survival analysis, methylation analysis, pivot analysis, and enrichment analysis, some important molecules and related function or pathway were identified to elucidate potential mechanism in esophageal cancer. Results: A total of 7457 DEGs and 14 gene interaction modules were identified. These module genes were significantly involved in the positive regulation of protein transport, gastric acid secretion, insulin-like growth factor receptor binding and other biological processes (BPs), as well as p53 signaling pathway, ERBB signaling pathway and epidermal growth factor receptor (EGFR) signaling pathway. Then, transcription factors (TFs) (including HIF1A) and ncRNAs (including CRNDE and hsa-mir-330-3p) significantly regulate dysfunction modules were identified. Further, survival analysis showed that GNGT2 was closely related to survival of esophageal cancer. And DEGs with strong methylation regulation ability were identified, including SST and SH3GL2. Conclusion: These works not only help us to reveal the potential regulatory factors in the development of disease, but also deepen our understanding of its deterioration mechanism.
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Ni J, Chen Y, Fei B, Zhu Y, Du Y, Liu L, Guo L, Zhu W. MicroRNA-301a Promotes Cell Proliferation and Resistance to Apoptosis through PTEN/PI3K/Akt Signaling Pathway in Human Ovarian Cancer. Gynecol Obstet Invest 2021; 86:108-116. [PMID: 33596588 DOI: 10.1159/000513070] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 08/23/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND MicroRNAs are endogenous small noncoding RNAs, which play a critical role in regulating various biological and pathologic processes. Furthermore, miR-301a has been detected to be overly expressed in tumorigenic progression of ovarian cancer. However, the effects of miR-301a on ovarian cancer are still unclear. OBJECTIVE The objective of this study is to investigate the molecular mechanisms of miR-301a in epithelial ovarian cancer cells. METHODS The miR-301a expression in ovarian cancer cells was detected. Then, cell proliferation, cell cycle, and apoptosis of the miR-301a-mimic-transfected ovarian cancer cells were determined, as well as the effects of the miR-301a mimic on the PTEN/phosphoinositide 3-kinase (PI3K) signaling pathway were explored. RESULTS We found that the miR-301a expression levels were markedly upregulated in ovarian cancer tissues and cells, and upregulation of miR-301a-promoted cell viability and proliferation. Our results also showed that the miR-301a-mimic accelerated cell cycle progression of ovarian cancer cells by targeting the CDK4/Cyclin-D1 pathway but not the CDK2/Cyclin-E pathway. Moreover, transfection of the miR-301a mimic into ovarian cancer cells could decrease the PTEN expression while increasing the PI3K and Akt phosphorylation, as compared with the miR-301a inhibitor group and the negative control group. CONCLUSION Therefore, miR-301a should be an oncogene in ovarian cancer, and overexpression of miR-301a promoted proliferation of ovarian cancer cells by modulating the PTEN/PI3K/Akt signaling pathway.
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Affiliation(s)
- Jie Ni
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Ying Chen
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Beibei Fei
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yan Zhu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yibei Du
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Lifen Liu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Liangsheng Guo
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Weipei Zhu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China,
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Cui Y, Huang S, Cao J, Ye J, Huang H, Liao D, Yang Y, Chen W, Pu R. Combined targeting of vascular endothelial growth factor C (VEGFC) and P65 using miR-27b-3p agomir and lipoteichoic acid in the treatment of gastric cancer. J Gastrointest Oncol 2021; 12:121-132. [PMID: 33708430 DOI: 10.21037/jgo-21-12] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Gastric cancer is the second leading cancer-related mortality worldwide and more effective treatment strategies are urgently needed to combat the disease. Using lipoteichoic acid (LTA) and miR-27b-3p agomir, we aimed to assess the efficacy of this combination of therapies in treating gastric cancer. Methods The RNA levels of miR-27b-3p, FOXO3, MET, KRAS, vascular endothelial growth factor C (VEGFC), TSC1, and P65 were analyzed by quantified-PCR (Q-PCR) and the cell viability of AGS cells was analyzed by MTT. Confirm Luciferase reporter assays were used to explore the putative miR-27b-3p binding sites and Western blot analyzed the protein level of GAPDH, VEGFC, P65, AKT, and phosphorylated-AKT (p-AKT). The level of P65 in both the cytoplasm and nucleus of AGS cells was visualized by immunofluorescence assay. Subcutaneous xenograft models of gastric cancer were established, and mice were treated with miR-27b-3p agomir, LTA, or both. Hematoxylin-eosin staining and Ki-67 immunohistochemistry analysis of tumor tissues were then performed. Results The results showed that the decreased expression of miR-27b-3p in gastric cancer cell lines inhibited the viability of AGS cells, and VEGFC was confirmed as the target of miR-27b-3p. In addition, ectopic expression of miR-27b-3p significantly inhibited the AKT pathway in AGS and N87 cells, and LTA suppressed the proliferation of gastric cancer cells by inhibiting the NF-κB pathway. In an established xenograft model, both miR-27b-3p agomir alone and LTA treatment alone inhibited tumor growth and treatment which combined the two showed an even stronger inhibitory effect. Conclusions Taken together, the combined use of LTA and miR-27b-3p agomir exhibited a synergistic effect in the treatment of gastric cancer.
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Affiliation(s)
- Yejia Cui
- Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
| | - Shaolong Huang
- Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China.,Department of Clinical Laboratory, Binhaiwan Central Hospital of Dongguan, Dongguan, China
| | - Jin Cao
- Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
| | - Jinjun Ye
- Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
| | - Haohai Huang
- Department of Clinical Pharmacy, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
| | - Dan Liao
- Department of Gynecology and Obstetrics, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
| | - Yufeng Yang
- Department of Pathology, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
| | - Wanchan Chen
- Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
| | - Rong Pu
- Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China
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Wang Q, Yu G, He H, Zheng Z, Li X, Lin R, Xu D. Differential expression of circular RNAs in bone marrow-derived exosomes from essential thrombocythemia patients. Cell Biol Int 2020; 45:869-881. [PMID: 33325145 DOI: 10.1002/cbin.11534] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 11/19/2020] [Accepted: 12/13/2020] [Indexed: 12/12/2022]
Abstract
Circular RNAs (circRNA) are closely associated with the pathogenesis of various hematological diseases. However, little is known about the potential functions of circRNAs in essential thrombocythemia (ET) development. The circRNA profile alterations in the bone marrow of ET patients were mainly investigated in this study. The sizes of exosomes derived from human bone marrow tissues were validated by the nanoparticle tracking analysis (NTA) method. CD63 and TSG101 expressions in exosomes were analyzed by western blot analysis. The profiles and differential expression of circRNAs in bone-derived exosomes were characterized by high-throughput sequencing. Herein, circular structures and expression of circRNAs were verified by Sanger sequencing and real-time polymerase chain reaction, respectively. The circRNA-miRNA-mRNA networks were predicted using the Cytoscape software. And we detected the effect of circ_0014614 on the transformation of K562 cells into megakaryocytes. Exosomes derived from the bone marrow of ET patients and healthy volunteers showed a diameter between 70 and 140 nm and expressed high CD63 and TSG101. Meanwhile, the circRNA profiles were significantly altered in bone marrow-derived exosomes from ET patients, among which circDAP3, circASXL1, and circRUNX1 were significantly downregulated in ET patients, thus conferring a new insight into the role of circRNAs in the pathogenesis of ET. Besides this, circRNA-encoding genes and miRNA-mRNA networks targeted by this three circRNA were involved in various biological processes and signaling pathways. And circ_0014614 could inhibit K562 cells' differentiation into megakaryocytes. The predictions of the potential function of these three differentially expressed circRNAs along with their interaction with specific miRNAs could provide a basis for circRNA-based ET diagnosis and treatment.
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Affiliation(s)
- Qiang Wang
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Guopan Yu
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Han He
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhongxin Zheng
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xuan Li
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ren Lin
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Dan Xu
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Cao HL, Gu MQ, Sun Z, Chen ZJ. miR-144-3p Contributes to the Development of Thyroid Tumors Through the PTEN/PI3K/AKT Pathway. Cancer Manag Res 2020; 12:9845-9855. [PMID: 33116843 PMCID: PMC7553603 DOI: 10.2147/cmar.s265196] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/28/2020] [Indexed: 12/17/2022] Open
Abstract
Purpose To explore the expression and related mechanism of miR-144-3p and PTEN in thyroid cancer (TC). Patients and Methods From February 2018 to November 2019, 62 patients with TC who received treatment in Chengwu Hospital Affiliated to Shandong First Medical University were collected. TC cells and human normal thyroid HTori-3 cells were purchased. The miR-144-3p-inhibitor, miR-144-3p-mimics, empty vector plasmid (miRNA-NC), si-PTEN and sh-PTEN were transfected into B-CPAP and HTh-7 cells. The expressions of miR-144-3p and PTEN in the specimens were tested by qRT-PCR (qP). WB was used to detect the expression of Bcl-2, APR3, N-cadherin, Slug and Bax proteins in the cells. The cell proliferation was detected by MTT, and the cell invasion was tested by Transwell. The apoptosis was detected by flow cytometry (FC). Results miR-144-3p was highly expressed and PTEN was weakly expressed in the patients’ tissues. The AUC of miR-144-3p and PTEN was >0.8. miR-144-3p and PTEN were related to TNM stage, lymph node metastasis and differentiation degree of TC patients. The B-CPAP and HTh-7 with the greatest expression differences were selected for transfection. The expression of miR-144-3p in miR-144-3p-inhibitor group was significantly lower than that in NC group (P<0.01), and that in miR-144-3p-mimics group was significantly higher than that in NC group (p < 0.01). The expression of PTEN in si-PTEN group was significantly lower than that in NC group (P<0.01), while that in sh-PTEN group was significantly higher than that in NC group (P<0.01). Silencing miR-144-3p and overexpressing PTEN could inhibit cell proliferation, invasion and promote apoptosis. WB detection uncovered that silencing the miR-144-3p expression and overexpressing PTEN could inhibit the PI3K, Akt, p-AKT, Bcl-2, APR3 and cyclinD1 proteins and promote the up-regulation of Bax expression. Rescue experiments revealed that the cell proliferation, invasion and apoptosis were not different from NC after co-transfection of miR-144-3p-mimics+sh-PTEN and miR-144-3p-inhibitor+si-PTEN into B-CPAP and HTh-7. Conclusion Inhibition of miR-144-3p expression can up-regulate PTEN and affect cell proliferation, invasion and apoptosis, which may be a potential therapeutic target for TC.
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Affiliation(s)
- Hui-Ling Cao
- Department of Head and Neck Surgery, Chengwu Hospital Affiliated to Shandong First Medical University, Heze, Shandong, 274200, People's Republic of China
| | - Ming-Qiang Gu
- Department of General Surgery, Chengwu Hospital Affiliated to Shandong First Medical University, Heze, Shandong, 274200, People's Republic of China
| | - Zhuo Sun
- Department of Oncology, Chengwu Hospital Affiliated to Shandong First Medical University, Heze, Shandong, 274200, People's Republic of China
| | - Zhong-Jian Chen
- Department of General Surgery, Chengwu Hospital Affiliated to Shandong First Medical University, Heze, Shandong, 274200, People's Republic of China
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Zheng M, Wu Y. Piceatannol suppresses proliferation and induces apoptosis by regulation of the microRNA‑21/phosphatase and tensin homolog/protein kinase B signaling pathway in osteosarcoma cells. Mol Med Rep 2020; 22:3985-3993. [PMID: 32901863 PMCID: PMC7533446 DOI: 10.3892/mmr.2020.11484] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 08/22/2019] [Indexed: 12/13/2022] Open
Abstract
Piceatannol (Pice), a natural analog of resveratrol, has been identified as an anticancer agent in various cancers by modulating the expression of microRNAs (miRNAs/miRs). However, the molecular mechanisms underlying the anticancer effects of Pice in osteosarcoma (OS) cells remain unclear. Thus, we hypothesized that Pice exerts anticancer effects on OS cells via the regulation of miRNA expression. Herein, we performed a MTT assay and flow cytometric analysis to determine cell viability and apoptosis in OS cells treated with Pice, respectively. Our results showed that Pice inhibits proliferation in a dose-dependent manner induces the apoptosis of OS cells. More importantly, miRNA microarray analysis identified that Pice alters miRNA expression profiles in human OS cells after treatment with Pice, and miR-21 was the most significantly downregulated. In addition, the therapeutic effects of Pice on OS cells were weakened by restoration of miR-21. In addition, we further verified that phosphatase and tensin homolog (PTEN), a tumor suppressor gene, is the functional target of miR-21 and Pice blocks the PTEN/AKT signaling pathway through inhibiting miR-21 expression in OS cells. Our findings suggested that Pice may exert anticancer effects on OS cells via mediating the miR-21/PTEN/AKT signaling pathway and could be considered to be a potential anticancer agent for treating OS.
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Affiliation(s)
- Mingyue Zheng
- Department of Acu‑mox and Tuina, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China
| | - Yaochi Wu
- Department of Acu‑mox and Tuina, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China
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miR-21-5p: A viable therapeutic strategy for regulating intraocular pressure. Exp Eye Res 2020; 200:108197. [PMID: 32871166 DOI: 10.1016/j.exer.2020.108197] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 08/03/2020] [Accepted: 08/13/2020] [Indexed: 12/20/2022]
Abstract
Lowering intraocular pressure (IOP) is the most effective treatment of glaucoma, however most of the current available glaucoma drugs target a single molecule. MicroRNAs (miRNAs) are noncoding RNAs that target a network of molecules. This study aims to investigate the role of miR-21-5p in regulating IOP and the mechanism of function. miR-21-5p mimics was topically applied to C57/BL6 mouse eyes, which significantly increased miR-21-5p expression in the conventional outflow tissue and reduced IOP by a maximum of 17.77% at 24 h after treatment. The conventional outflow facility measured by ex vivo moue eye perfusion of miR-21-5p was significantly increased by 60.14%. Moreover, miR-21-5p overexpression significantly reduced the transendothelial electrical resistance in porcine angular aqueous plexus cells. Transcriptome analysis and further quantification by Western blot and PCR revealed that SMAD7 and FGF18 might be the downstream target of miR-21-5p in regulating aqueous humor outflow. The predicted functional pathways PTEN/eNOS, RhoB/pMLC and TIMP3/MMP9 were significantly altered after miR-21-5p transfection. Dual luciferase assay verified the direct targets of miR-21-5p. In conclusion, miR-21-5p seems to regulate IOP by modulating multiple genes that are associated with aqueous humor outflow, including genes those regulating cell adhesion, cytoskeletal dynamics and extracellular matrix turnover. Thus, miR-21-5p represents a new therapeutic strategy for glaucoma and a viable alternative to existing multidrug regimens.
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Ren X, Jing YX, Zhou ZW, Yang QM. MiR-17-5p inhibits cerebral hypoxia/reoxygenationinjury by targeting PTEN through regulation of PI3K/AKT/mTOR signaling pathway. Int J Neurosci 2020; 132:192-200. [PMID: 32762281 DOI: 10.1080/00207454.2020.1806836] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To investigate the role and mechanism of miR-17-5p in cerebral hypoxia/reoxygenation (H/R)-induced apoptosis. METHODS The present study used human brain microvascular endothelial cells (HBMVECs) to establish cerebral H/R model. MTT was used to measure the cell viability. Flow cytometry was used to detect the cell apoptosis. The interaction between miR-17-5p and PTEN was determined using dual luciferase reporter assay. RT-qPCR and Western blotting were used for determination of the expression of miR-17-5p, PTEN, apoptosis- and PI3K/AKT/mTOR signalling-related proteins. RESULTS The cell viability and the expression of miR-17-5p were obviously down-regulated while the expression of PTEN was obviously up-regulated in H/R cells. The cell viability was remarkably enhanced, and the cell apoptosis induced by H/R injury was dramatically reduced when miR-17-5p was overexpressed in HBMVECs under H/R condition, which was reversed by overexpression of PTEN. Dual luciferase reporter assay showed PTEN was a direct target of miR-17-5p. Treatment of PI3K inhibitor LY294002 significantly increased the apoptosis rate of HBMVECs, and this effect was significantly reversed by transfection of miR-17-5p mimics, while further dramatically enhanced by overexpression of PTEN. CONCLUSION MiR-17-5p could ameliorate cerebral I/R injury-induced cell apoptosis by directly targeting PTEN and regulation of PI3K/AKT/mTOR signalling.
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Affiliation(s)
- Xiang Ren
- Department of Neurology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, PR China
| | - Ying-Xia Jing
- Department of Emergency, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, PR China
| | - Zhi-Wen Zhou
- Department of Neurology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, PR China
| | - Qi-Ming Yang
- Department of Neurology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, PR China
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Aali M, Mesgarzadeh AH, Najjary S, Abdolahi HM, Kojabad AB, Baradaran B. Evaluating the role of microRNAs alterations in oral squamous cell carcinoma. Gene 2020; 757:144936. [PMID: 32640301 DOI: 10.1016/j.gene.2020.144936] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 05/31/2020] [Accepted: 07/01/2020] [Indexed: 12/16/2022]
Abstract
Oral squamous cell carcinoma (OSCC) accounts for nearly 90 percent of oral cavity malignancies and is one of the most widespread oral cancers in the world. The microRNAs (miRNAs or miRs) have an important role in cellular processes comprising cell cycle, differentiation, and also apoptosis. MiRNAs are also implicated in the progression of cancers, including OSCC, through a variety of signaling pathways. One of the most significant signaling pathways in OSCC is the PI3K / Akt pathway that has been illustrated to be under the tight regulation of miRNAs. Deregulation or activation of the PI3K / Akt pathway due to mutations has been revealed to be implicated in the development of oral cancer. According to studies, more than 47% of HNSCC and around 38% of OSCC samples indicate at least one molecular alteration in this signaling pathway. The potential of miRNAs for their use as therapeutic tools in the diagnosis as well as treatment of numerous diseases have been confirmed. In the current review, we summarize miRNAs and their possible mechanisms as well as their functions in OSCC advancement and progression.
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Affiliation(s)
- Mehdi Aali
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran; Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Hossein Mesgarzadeh
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran; Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shiva Najjary
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Mashhadi Abdolahi
- Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Chen S, Yang S, Wang M, Chen J, Huang S, Wei Z, Cheng Z, Wang H, Long M, Li P. Curcumin inhibits zearalenone-induced apoptosis and oxidative stress in Leydig cells via modulation of the PTEN/Nrf2/Bip signaling pathway. Food Chem Toxicol 2020; 141:111385. [DOI: 10.1016/j.fct.2020.111385] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/29/2020] [Accepted: 04/19/2020] [Indexed: 12/15/2022]
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A Driver Never Works Alone-Interplay Networks of Mutant p53, MYC, RAS, and Other Universal Oncogenic Drivers in Human Cancer. Cancers (Basel) 2020; 12:cancers12061532. [PMID: 32545208 PMCID: PMC7353041 DOI: 10.3390/cancers12061532] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/03/2020] [Accepted: 06/05/2020] [Indexed: 12/12/2022] Open
Abstract
The knowledge accumulating on the occurrence and mechanisms of the activation of oncogenes in human neoplasia necessitates an increasingly detailed understanding of their systemic interactions. None of the known oncogenic drivers work in isolation from the other oncogenic pathways. The cooperation between these pathways is an indispensable element of a multistep carcinogenesis, which apart from inactivation of tumor suppressors, always includes the activation of two or more proto-oncogenes. In this review we focus on representative examples of the interaction of major oncogenic drivers with one another. The drivers are selected according to the following criteria: (1) the highest frequency of known activation in human neoplasia (by mutations or otherwise), (2) activation in a wide range of neoplasia types (universality) and (3) as a part of a distinguishable pathway, (4) being a known cause of phenotypic addiction of neoplastic cells and thus a promising therapeutic target. Each of these universal oncogenic factors—mutant p53, KRAS and CMYC proteins, telomerase ribonucleoprotein, proteasome machinery, HSP molecular chaperones, NF-κB and WNT pathways, AP-1 and YAP/TAZ transcription factors and non-coding RNAs—has a vast network of molecular interrelations and common partners. Understanding this network allows for the hunt for novel therapeutic targets and protocols to counteract drug resistance in a clinical neoplasia treatment.
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Ghafouri‐Fard S, Shoorei H, Dashti S, Branicki W, Taheri M. Expression profile of lncRNAs and miRNAs in esophageal cancer: Implications in diagnosis, prognosis, and therapeutic response. J Cell Physiol 2020; 235:9269-9290. [DOI: 10.1002/jcp.29825] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 05/11/2020] [Accepted: 05/18/2020] [Indexed: 12/24/2022]
Affiliation(s)
- Soudeh Ghafouri‐Fard
- Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Hamed Shoorei
- Department of Anatomical Sciences Birjand University of Medical Sciences Birjand Iran
| | - Sepideh Dashti
- Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Wojciech Branicki
- Malopolska Centre of Biotechnology, Jagiellonian University Kraków Poland
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences Tehran Iran
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Zhai K, Liskova A, Kubatka P, Büsselberg D. Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells. Int J Mol Sci 2020; 21:E4177. [PMID: 32545311 PMCID: PMC7312732 DOI: 10.3390/ijms21114177] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/05/2020] [Accepted: 06/08/2020] [Indexed: 02/06/2023] Open
Abstract
Intracellular calcium (Ca2+) concentration ([Ca2+]i) is a key determinant of cell fate and is implicated in carcinogenesis. Membrane ion channels are structures through which ions enter or exit the cell, depending on the driving forces. The opening of transient receptor potential vanilloid 1 (TRPV1) ligand-gated ion channels facilitates transmembrane Ca2+ and Na+ entry, which modifies the delicate balance between apoptotic and proliferative signaling pathways. Proliferation is upregulated through two mechanisms: (1) ATP binding to the G-protein-coupled receptor P2Y2, commencing a kinase signaling cascade that activates the serine-threonine kinase Akt, and (2) the transactivation of the epidermal growth factor receptor (EGFR), leading to a series of protein signals that activate the extracellular signal-regulated kinases (ERK) 1/2. The TRPV1-apoptosis pathway involves Ca2+ influx and efflux between the cytosol, mitochondria, and endoplasmic reticulum (ER), the release of apoptosis-inducing factor (AIF) and cytochrome c from the mitochondria, caspase activation, and DNA fragmentation and condensation. While proliferative mechanisms are typically upregulated in cancerous tissues, shifting the balance to favor apoptosis could support anti-cancer therapies. TRPV1, through [Ca2+]i signaling, influences cancer cell fate; therefore, the modulation of the TRPV1-enforced proliferation-apoptosis balance is a promising avenue in developing anti-cancer therapies and overcoming cancer drug resistance. As such, this review characterizes and evaluates the role of TRPV1 in cell death and survival, in the interest of identifying mechanistic targets for drug discovery.
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Affiliation(s)
- Kevin Zhai
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, PO Box 24144, Qatar;
| | - Alena Liskova
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, PO Box 24144, Qatar;
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Pasi F, Corbella F, Baio A, Capelli E, De Silvestri A, Tinelli C, Nano R. Radiation-induced circulating miRNA expression in blood of head and neck cancer patients. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2020; 59:237-244. [PMID: 32040721 DOI: 10.1007/s00411-020-00832-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 01/25/2020] [Indexed: 06/10/2023]
Abstract
In recent years, scientists have found evidence confirming the aberrant expression of miRNAs in cancer patients compared to healthy individuals. The growing interest in the identification of non-invasive and specific diagnostic and prognostic molecular markers has identified microRNAs as potential candidates in cancer diagnosis, prognosis and treatment response. In the present study, we have analyzed the expression profile of circulating miR-21, -191 and -421 in peripheral blood of head and neck cancer patients (HNC) to investigate a possible modulation of mRNA levels by radiation and to identify the role of mRNA as biomarkers of cancer prognosis. Results showed a modulation of the microRNA expression at different time points after radiotherapy, suggesting that treatment may influence the release of circulating miRNAs depending also on the time interval elapsed since radiotherapy. The expression levels of miR-21, -191 and -421 were higher in blood of patients treated with radiotherapy alone after 6 months from the end of therapy and high levels of them seemed to correlate with the remission of the disease. The trends shown in this study confirmed that miRNAs could be useful prognosis markers and could provide preliminary data for further evaluation in predicting patients' response to radiotherapy by developing miRNA-based treatments to improve the sensitivity of cancer cells to radiotherapy.
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Affiliation(s)
- Francesca Pasi
- Radiotherapy Unit, Department of Oncohaematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, Pavia, Italy.
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Ferrata 9, Pavia, Italy.
| | - Franco Corbella
- Radiotherapy Unit, Department of Oncohaematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, Pavia, Italy
| | - Ambrogia Baio
- Radiotherapy Unit, Department of Oncohaematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, Pavia, Italy
| | - Enrica Capelli
- Department of Earth and Environmental Sciences, Laboratory of Immunology and Genetic Analysis, University of Pavia, Via Taramelli 21, Pavia, Italy
| | | | - Carmine Tinelli
- Biometry and Medical Statistics, Policlinico San Matteo di Pavia, Pavia, Italy
| | - Rosanna Nano
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Ferrata 9, Pavia, Italy
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Sinomenine Inhibits Migration and Invasion of Human Lung Cancer Cell through Downregulating Expression of miR-21 and MMPs. Int J Mol Sci 2020; 21:ijms21093080. [PMID: 32349289 PMCID: PMC7247699 DOI: 10.3390/ijms21093080] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 04/24/2020] [Indexed: 02/06/2023] Open
Abstract
Sinomenine is an alkaloid derived from Sinomenium acutum. Recent studies have found that sinomenine can inhibit various cancers by inhibiting the proliferation, migration and invasion of tumors and inducing apoptosis. This study aims to investigate the effect and mechanism of sinomenine on inhibiting the migration and invasion of human lung adenocarcinoma cells in vitro. The results demonstrate that viabilities of A549 and H1299 cells were inhibited by sinomenine in a dose-dependent manner. When treated with sub-toxic doses of sinomenine, cell migration and invasion are markedly suppressed. Sinomenine decreases the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9, and the extracellular inducer of matrix metalloproteinase (EMMPRIN/CD147), but elevates the expression of reversion-inducing cysteine-rich proteins with kazal motifs (RECK) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. In addition, sinomenine significantly increases the expression of the epithelial marker E-cadherin but concomitantly decreases the expression of the mesenchymal marker vimentin, suggesting that it suppresses epithelial–mesenchymal transition (EMT). Moreover, sinomenine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. The downregulation of miR-21 decreases cell invasion, while the upregulation of miR-21 increases cell invasion. Furthermore, the downregulation of miR-21 stimulates the expression of RECK, TIMP-1/-2, and E-cadherin, but reduces the expression of MMP-2/-9, EMMPRIN/CD147, and vimentin. Taken together, the results reveal that the inhibition of A549 cell invasion by sinomenine may, at least in part, be through the downregulating expression of MMPs and miR-21. These findings demonstrate an attractive therapeutic potential for sinomenine in lung cancer anti-metastatic therapy.
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Wang S, Ma F, Feng Y, Liu T, He S. Role of exosomal miR‑21 in the tumor microenvironment and osteosarcoma tumorigenesis and progression (Review). Int J Oncol 2020; 56:1055-1063. [PMID: 32319566 DOI: 10.3892/ijo.2020.4992] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 02/07/2020] [Indexed: 11/06/2022] Open
Abstract
Osteosarcoma is the most common bone tumor affecting both adolescents and children. Early detection is critical for the effective treatment of the disease. Derived from cancer cells, miR‑21 contained within exosomes in the tumor microenvironment may act on both cancer cells and the surrounding tumor microenvironment (TME), including immune cells, endothelial cells and fibroblasts. In human serum and plasm, the level of exosomal miR‑21 between osteosarcoma patients and healthy controls differs, supporting the role of miR‑21 as a biomarker for osteosarcoma. The involvement of a number of miR‑21 target genes in tumor progression suggests that miR‑21 may significantly affect the plasticity of cancer cells, leading to tumor progression, metastasis, angiogenesis and immune escape in osteosarcoma. Understanding the biogenesis and functions of exosomal miR‑21 is of great value for the diagnosis and therapy of cancer, including osteosarcoma. The present review discusses the role of miR‑21 in the tumor microenvironment, and in the development and progression of osteosarcoma, with an aim to summarize the functions of this miRNA in cancer.
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Affiliation(s)
- Shoufeng Wang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China
| | - Fang Ma
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China
| | - Yi Feng
- Ovarian Cancer Research, Perelman School of Medicine, University of Pennsylvania, Philadephia, PA 19104, USA
| | - Tang Liu
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China
| | - Shasha He
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China
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Jafarzadeh M, Soltani BM, Soleimani M, Hosseinkhani S. Epigenetically silenced LINC02381 functions as a tumor suppressor by regulating PI3K-Akt signaling pathway. Biochimie 2020; 171-172:63-71. [DOI: 10.1016/j.biochi.2020.02.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 02/18/2020] [Indexed: 12/21/2022]
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Yao J, Xu M, Liu Z. Rapamycin inhibits proliferation and apoptosis of retinoblastoma cells through PI3K/AKT signaling pathway. Oncol Lett 2020; 19:2950-2956. [PMID: 32218850 PMCID: PMC7068238 DOI: 10.3892/ol.2020.11363] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 12/03/2019] [Indexed: 11/23/2022] Open
Abstract
Effects of Rapamycin on the proliferation and apoptosis of retinoblastoma cells through the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT) signaling pathway were studied. The retinoblastoma Y79 cells were selected and divided into negative control group (NC group), 0.2 µM Rapamycin group and 0.4 µM Rapamycin group. Then the proliferative activity of Y79 cells was detected using Cell Counting Kit-8 (CCK8) assay, the content of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) in cells in each group was detected using enzyme-linked immunosorbent assay (ELISA), and the apoptosis of Y79 cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the changes in Y79 cell cycle and apoptosis were determined through flow cytometry, and apoptosis and PI3K/AKT pathway were detected using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. It was found that the number of cells and the proliferative activity were significantly reduced in 0.2 µM Rapamycin group and 0.4 µM Rapamycin group. In 0.2 µM Rapamycin group and 0.4 µM Rapamycin group, the content of ROS and MDA was significantly decreased, while that of SOD was notably increased. TUNEL assay and flow cytometry showed that in 0.2 µM Rapamycin group and 0.4 µM Rapamycin group, the number of apoptotic cells was obviously increased, and the cell cycle was basically arrested in S phase. The expression levels of Bcl-2, PI3K and AKT declined in 0.2 µM Rapamycin group and 0.4 µM Rapamycin group, whereas the expression of Caspase 8 increased. Similar results were also obtained in the protein assay. The above results were significantly superior in 0.4 µM Rapamycin group to those in 0.2 µM Rapamycin group. Rapamycin inhibits proliferation and promotes apoptosis of retinoblastoma cells through inhibiting the PI3K/AKT signaling pathway.
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Affiliation(s)
- Jun Yao
- Department of Ophthalmology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China
| | - Min Xu
- Department of Otorhinolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi 710004, P.R. China
| | - Ziyao Liu
- Department of Ophthalmology, The Second Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi 710004, P.R. China
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Zhang X, Liu C, Li H, Guo L. Effects of miR-21 on proliferation and apoptosis of WT cells via PTEN/Akt pathway. Exp Ther Med 2020; 19:2155-2160. [PMID: 32104279 PMCID: PMC7027200 DOI: 10.3892/etm.2019.8376] [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] [Received: 10/18/2019] [Accepted: 12/13/2019] [Indexed: 12/29/2022] Open
Abstract
Micro ribonucleic acid (miR)-21 in the proliferation and apoptosis of Wilms' tumor (WT) cells was explored. SK-NEP-1 cells were transfected with miR-21 inhibitor to silence the expression of miR-21. Then, the effects of miR-21 silencing on the proliferation and apoptosis of WT SK-NEP-1 cells were detected through cell counting kit-8 (CCK-8), colony formation assay and flow cytometry. The targets of miR-21 were analyzed via TargetScan database. Fluorescence real-time quantitative polymerase chain reaction (RT-qPCR) assay and western blot analysis were conducted to detect the changes in messenger RNA (mRNA) and protein expression levels of gene of phosphate and tension homology deleted on chromosome ten (PTEN) after silencing miR-21. Whether miR-21 directly binds to PTEN was examined by activity detection via dual luciferase reporter gene assay. Western blotting was employed to detect the correlation of miR-21 with PTEN and protein kinase B (Akt). Compared with normal control (NC) group, miR-21 inhibitor group had significantly inhibited proliferation of SK-NEP-1 cells (P<0.05), notably reduced number of clones (P<0.05) and overtly raised proportion of apoptotic cells (P<0.05). The suppression of miR-21 expression upregulated the mRNA and protein expression levels of PTEN, and the results of activity detection via dual luciferase reporter gene assay indicated that miR-21 bound to PTEN 3'-untranslated region (UTR) to repress its expression (P<0.05). PTEN silencing increased phosphorylated Akt (p-Akt) level in SK-NEP-1 cells, but there was no changes in Akt protein level. After silencing both PTEN and miR-21, the decrease in p-Akt was reversed, thereby reversing the inhibitory effect of miR-21 on the proliferation of SK-NEP-1 cells (P<0.05). miR-21 affects the proliferation and apoptosis of WT SK-NEP-1 cells via the PTEN/Akt pathway.
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Affiliation(s)
- Xiuli Zhang
- Pediatrics Intensive Care Unit, Shanxian Central Hospital, Heze, Shandong 274300, P.R. China
| | - Chunyan Liu
- Pediatrics Intensive Care Unit, Shanxian Central Hospital, Heze, Shandong 274300, P.R. China
| | - Haiyan Li
- Pediatrics Intensive Care Unit, Shanxian Central Hospital, Heze, Shandong 274300, P.R. China
| | - Li Guo
- Pediatrics Intensive Care Unit, Shanxian Central Hospital, Heze, Shandong 274300, P.R. China
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Wang L, Yin Z, Wang F, Han Z, Wang Y, Huang S, Hu T, Guo M, Lei P. Hydrogen exerts neuroprotection by activation of the miR-21/PI3K/AKT/GSK-3β pathway in an in vitro model of traumatic brain injury. J Cell Mol Med 2020; 24:4061-4071. [PMID: 32108985 PMCID: PMC7171410 DOI: 10.1111/jcmm.15051] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 10/11/2019] [Accepted: 01/06/2020] [Indexed: 12/26/2022] Open
Abstract
Few studies have explored the effect of hydrogen on neuronal apoptosis or impaired nerve regeneration after traumatic brain injury, and the mechanisms involved in these processes are unclear. In this study, we explored neuroprotection of hydrogen‐rich medium through activation of the miR‐21/PI3K/AKT/GSK‐3β pathway in an in vitro model of traumatic brain injury. Such model adopted PC12 cells with manual scratching. Then, injured cells were cultured in hydrogen‐rich medium for 48 hours. Expression of miR‐21, p‐PI3K, p‐Akt, p‐GSK‐3β, Bax and Bcl‐2 was measured using RT‐qPCR, Western blot analysis and immunofluorescence staining. Rate of apoptosis was determined using TUNEL staining. Neuronal regeneration was assessed using immunofluorescence staining. The results showed that hydrogen‐rich medium improved neurite regeneration and inhibited apoptosis in the injured cells. Scratch injury was accompanied by up‐regulation of miR‐21, p‐PI3K, p‐Akt and p‐GSK‐3β. A miR‐21 antagomir inhibited the expression of these four molecules, while a PI3K blocker only affected the three proteins and not miR‐21. Both the miR‐21 antagomir and PI3K blocker reversed the protective effect of hydrogen. In conclusion, hydrogen exerted a neuroprotective effect against neuronal apoptosis and impaired nerve regeneration through activation of miR‐21/PI3K/AKT/GSK‐3β signalling in this in vitro model of traumatic brain injury.
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Affiliation(s)
- Lu Wang
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Zhenyu Yin
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Feng Wang
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Zhaoli Han
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Yifeng Wang
- Department of Intensive Care Unit, Tianjin Medical University General Hospital, Tianjin, China
| | - Shan Huang
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Tianpeng Hu
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Mengtian Guo
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Ping Lei
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
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Yang Y, Li G. Retracted: Icariin inhibits proliferation, migration, and invasion of medulloblastoma DAOY cells by regulation of SPARC. Phytother Res 2020; 34:591-600. [PMID: 32011040 DOI: 10.1002/ptr.6545] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 09/12/2019] [Accepted: 10/22/2019] [Indexed: 12/29/2022]
Affiliation(s)
- Yan Yang
- Department of NeurosurgeryJining No.1 People's Hospital Jining China
| | - Guifang Li
- Department of Occupational MedicineWeifang People's Hospital Weifang China
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Song Y, Cui X, Zhao R, Hu L, Li Y, Liu C. Emodin protects against lipopolysaccharide-induced inflammatory injury in HaCaT cells through upregulation of miR-21. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:2654-2661. [PMID: 31250665 DOI: 10.1080/21691401.2019.1629951] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Background/aim: Pressure ulcers are a disastrous health issue in which inflammation is involved. Emodin possesses biological properties in inflammation. Our study investigated functions of emodin in lipopolysaccharide (LPS)-treated HaCaT cells. Methods: LPS was used to induce cell inflammation. MTT and flow cytometry were applied for cell viability and apoptosis assays, respectively. Moreover, apoptotic proteins were detected by western blot. Similarly, inflammatory factors and signalling related proteins were also determined by western blot. Results: Emodin increased cell viability and diminished apoptosis in LPS-treated HaCaT cells. Moreover, cleaved-PARP, cleaved-caspase-3 and cleaved-caspase-9 were all downregulated by emodin. Furthermore, inflammatory factors IL-1β, IL-6, Cox-2 and iNOS were inhibited by emodin in LPS-treated cells. In addition, emodin decreased phosphorylation of p65 and IκBα and the level of PTEN while enhanced phosphorylation of PI3K and AKT. Importantly, emodin increased expression of miR-21 suppressed by LPS and miR-21 downregulation negated the protective functions of emodin. Conclusions: Emodin promoted cell growth presented by increasing viability and blocking apoptosis process with inflammation inhibition. The protective activity of emodin was mediated by miR-21 up-regulation.
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Affiliation(s)
- Yanping Song
- a Department of Health Management, Heze Medical College , Heze , China
| | - Xueling Cui
- b Department of Breast and Thyroid Surgery, Heze Municipal Hospital , Heze , China
| | - Ruilan Zhao
- c Department of General Medicine, Heze Municipal Hospital , Heze , China
| | - Lanying Hu
- d Department of Joint Surgery, Heze Municipal Hospital , Heze , China
| | - Yanjun Li
- e e Department of Nursing, Heze Medical College , Heze , China
| | - Cuiling Liu
- b Department of Breast and Thyroid Surgery, Heze Municipal Hospital , Heze , China
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Liu W, Zhao ZM, Liu YL, Pan HF, Lin LZ. Weipiling ameliorates gastric precancerous lesions in Atp4a -/- mice. Altern Ther Health Med 2019; 19:318. [PMID: 31744486 PMCID: PMC6862855 DOI: 10.1186/s12906-019-2718-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 10/15/2019] [Indexed: 01/24/2023]
Abstract
Background Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4–17, 2014; Kim and Bae, Curr Opin Hematol 25:52–59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. Methods Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a−/− mouse model (Spicer etal., J Biol Chem 275:21555–21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a−/−mice. Results In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a−/− mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05). Conclusions Conclusively, WPL could ameliorate GPLs in Atp4a−/− mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.
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