MicroRNA-192 suppresses cell proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes by downregulating caveolin 1

• Published in: Molecular and cellular biochemistry Vol. 432; no. 1-2; pp. 123 - 130
• Main Authors: Li, Supin, Jin, Zhenmu, Lu, Xiaobing
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Analysis; Apoptosis; Arthritis; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Bcl-2 protein; Biochemistry; Biomedical and Life Sciences; Cardiology; Caspase; Caspase-3; Caveolin; Caveolin 1 - biosynthesis; Caveolin-1; Cell adhesion & migration; Cell cycle; Cell growth; Cell Proliferation; Cells, Cultured; Down-Regulation; Ectopic expression; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; G1 phase; Humans; Life Sciences; Luciferase; Male; Medical Biochemistry; MicroRNA; MicroRNAs; MicroRNAs - biosynthesis; Middle Aged; miRNA; Oncology; Pathogenesis; Restoration; Rheumatoid arthritis; Rheumatoid factor; Ribonucleic acid; RNA; Synoviocytes; Synoviocytes - metabolism; Synoviocytes - pathology; Target recognition; Fibroblast-like synoviocytes; MicroRNA; Rheumatoid arthritis; Therapeutic target; Apoptosis; Hyperproliferation
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-017-3003-3

Fibroblast-like synoviocytes (FLSs) play an important role in the pathogenesis of rheumatoid arthritis (RA). This study was conducted to explore the role of microRNA (miR)-192 in the regulation of the biology of RA-FLSs. The expression of miR-192 in RA and healthy synovial tissues was measured. The effects of overexpression of miR-192 on RA-FLS proliferation and apoptosis were investigated. Luciferase reporter assay and Western blot analysis were performed to identify direct target genes of miR-192. RA synovial tissues had significantly lower levels of miR-192 than healthy controls ( P  = 0.004). Moreover, miR-192 levels were 2.9-fold lower in RA-FLSs relative to normal human FLSs ( P  < 0.05). Ectopic expression of miR-192 significantly inhibited the proliferation and caused a cell cycle arrest at the G0/G1 phase in RA-FLSs. Moreover, miR-192 overexpression triggered apoptosis, which was accompanied by an increase in caspase-3 activity and Bax/Bcl-2 ratio. Caveolin 1 (CAV1) was identified to be a direct target of miR-192. Overexpression of miR-192 led to a reduction of endogenous CAV1 in RA-FLSs. Silencing of CAV1 significantly decreased cell proliferation and promoted apoptosis in RA-FLSs. Rescue experiments with a miR-192-resistant variant of CAV1 showed that enforced expression of CAV1 restored cell proliferation and attenuated apoptosis in miR-192-overexpressing RA-FLSs. In conclusion, miR-192 is downregulated in RA synovial tissues and restoration of its expression elicits growth-suppressive effects on RA-FLSs by targeting CAV1 . The miR-192/CAV1 pathway may represent a novel target for prevention and treatment of RA.