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

Abstract

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.

New signatures of poor CD4 cell recovery after suppressive antiretroviral therapy in HIV-1-infected individuals: involvement of miR-192, IL-6, sCD14 and miR-144

“…In line with our results, miR-192 has been reported to inhibit cell proliferation and induce apoptosis in vitro 39,40 and rheumatoid arthritis 41 . Also, p53 can induce miR-192 to promote its activation facilitating cell cycle arrest 42,43 .…”

Retracted: Lipopolysaccharides‐mediated injury to chondrogenic ATDC5 cells can be relieved by Sinomenine via downregulating microRNA‐192

“…To data, several miRNAs have been mentioned as downstream genes of SIN, including miR-101 (Liu, Man, & Zhao, 2018), miR-324-5p (Song et al, 2015), and miR-155 (Yu et al, 2013). miR-192 has been mentioned as a differentially expressed miRNA in rheumatoid arthritis synovial tissues, and its expression is associated with fibroblast-like synoviocytes growth (Li, Jin, & Lu, 2017). miR-192 expression is sensitivity to LPS stimulation (Zhang et al, 2015), and the physiological role of miR-192 in inflammatory system has been reported (Chu & Xu, 2016 et al (2015), which confirmed our hypothesis.…”

lncRNA CASC2 downregulation participates in rheumatoid arthritis, and CASC2 overexpression promotes the apoptosis of fibroblast‑like synoviocytes by downregulating IL‑17

“…HFLSs participate in the development and progression of RA by producing cytokines and proteases that contribute to cartilage destruction (18). Apoptosis of HFLSs is currently considered as a potential therapeutic target for RA (19,20). Our study observed that IL-17 inhibited HFLSs apoptosis, while lncRNA CASC2 promoted HFLSs apoptosis by inhibiting IL-17.…”