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

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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.

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Authors and Affiliations

  1. Department of Rheumatology, Wenzhou Central Hospital, Wenzhou, 325000, China

    Supin Li & Zhenmu Jin

  2. Department of Orthopedic Surgery, Yanghu Branch, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, No. 68, Gehu Zhong Road, Changzhou, 213164, China

    Xiaobing Lu

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  1. Supin Li
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Correspondence to Xiaobing Lu.

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Li, S., Jin, Z. & Lu, X. MicroRNA-192 suppresses cell proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes by downregulating caveolin 1. Mol Cell Biochem 432, 123–130 (2017). https://doi.org/10.1007/s11010-017-3003-3

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  • DOI: https://doi.org/10.1007/s11010-017-3003-3

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