MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway
Autor: | Zhixiang Huang, Xia Pan, Xin Guo, Xuechan Huang, Zhengping Huang, Shan Xing, Weiming Deng, Chiwei Wu, Meng Liu, Fan Feng, Y. Huang, Tian-wang Li, Yunqing Wang, Jiawei Jiang |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
musculoskeletal diseases Male rheumatoid arthritis PTEN Biophysics Biology Biochemistry Cell Line Arthritis Rheumatoid 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Cell Movement microRNA Tensin Humans skin and connective tissue diseases fibroblast-like synoviocytes Molecular Biology PI3K/AKT/mTOR pathway Research Articles Cell Proliferation Akt/PKB signaling pathway Microarray analysis techniques PTEN Phosphohydrolase miR-26a-5p Cell Biology Cell cycle Synoviocytes MicroRNAs 030104 developmental biology Gene Expression Regulation Apoptosis Tissue Array Analysis 030220 oncology & carcinogenesis Cancer research biology.protein Female Proto-Oncogene Proteins c-akt Signal Transduction Research Article |
Zdroj: | Bioscience Reports |
ISSN: | 1573-4935 |
Popis: | Behavior alterations in fibroblast-like synoviocytes (FLS) contribute to a pivotal role in pathogenesis of rheumatoid arthritis (RA). MiRNAs are closely involved in a variety of pathologic conditions. In the present study, we aimed to screen for the aberrant expression of miRNAs in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to further identify the altered expression of miR-26a-5p in RA-FLS and to investigate the role of miR-26a-5p in RA. The altered expression of miR-26a-5p in RA-FLS was screened by microarray analysis and confirmed by quantitative real time PCR. The effect of miR-26a-5p on proliferation, cell cycle, apoptosis, and invasion in RA-FLS were studied. The verification of miR-26a-5p target mRNA and downstream signaling pathway was elucidated by bioinformatics analysis, dual luciferase reporter assay, and western blot. Expression of miR-26a-5p was higher in RA-FLS than in fibroblast-like synoviocytes from osteoarthritis patients and trauma patients. Overexpression of miR-26a-5p RA-FLS promoted cells proliferation, G1/S transition, cells invasion, and resisted apoptosis in RA-FLS, whereas it led to contrary effects when inhibiting the expression of miR-26a-5p. The 3′UTR of tensin homolog (PTEN) was directly targetted by miR-26a-5p and activation of phosphoinositide 3-kinase (PI3K)/AKT pathway was observed when overexpression of miR-26a-5p. Our study suggested that miR-26a-5p has a complementary role in cells proliferation, invasion, and apoptosis of RA-FLS, which may be attributed to its activation effect on PI3K/AKT signaling pathway via targetting PTEN. MiR-26a-5p is likely to be a clinically helpful target for novel therapeutic strategies in RA. |
Databáze: | OpenAIRE |
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