MicroRNA-192 suppresses cell proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes by downregulating caveolin 1.
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.
Department of Rheumatology, Wenzhou Central Hospital, Wenzhou, 325000, China.
Supin
S
Li
Department of Rheumatology, Wenzhou Central Hospital, Wenzhou, 325000, China.
Zhenmu
Z
Jin
Department of Orthopedic Surgery, Yanghu Branch, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, No. 68, Gehu Zhong Road, Changzhou, 213164, China. Fyjk6789056@163.com.
Xiaobing
X
Lu
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D000070918:Synoviocytes / Q000378:metabolism* / Q000473:pathology
C495540:CAV1 protein, human; D051242:Caveolin 1; C546783:MIRN192 microRNA, human; D035683:MicroRNAs
Apoptosis; Fibroblast-like synoviocytes; Hyperproliferation; MicroRNA; Rheumatoid arthritis; Therapeutic target