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  • Title: Circ_0136474 promotes the progression of osteoarthritis by sponging mir-140-3p and upregulating MECP2.
    Author: Cheng S, Nie Z, Cao J, Peng H.
    Journal: J Mol Histol; 2023 Feb; 54(1):1-12. PubMed ID: 36435914.
    Abstract:
    BACKGROUND: Circular RNAs (circRNAs) have pivotal roles in the progression of many diseases, including osteoarthritis (OA). The detained function and regulatory mechanism of circ_0136474 in OA are still largely unknown. METHODS: The chondrocytes (CHON-001 cells) were exposed to interleukin-1 beta (IL-1β) to mimic the injury in OA. The expression levels of circ_0136474, microRNA-140-3p (miR-140-3p), methyl-CpG-binding protein 2 (MECP2) mRNA were measured by qRT-PCR. Cell proliferation was assessed using CCK-8 assay. Flow cytometry was employed for measuring cell apoptosis. All protein levels were evaluated via western blot analysis. ELISA was used for detecting the concentrations of the inflammatory cytokines. Dual-luciferase reporter analysis and RNA Immunoprecipitation analysis were conducted for confirming the association between miR-140-3p and circ_0136474 or MECP2. RESULTS: Circ_0136474 was upregulated in IL-1β-induced CHON-001 cells and OA cartilage tissues. Circ_0136474 deficiency alleviated IL-1β-stimulated CHON-001 cell damage via enhancing cell proliferation and reducing extracellular matrix (ECM) degradation, apoptosis, and inflammation. Circ_0136474 was a sponge of miR-140-3p, and miR-140-3p inhibition reversed the roles of circ_0136474 knockdown in IL-1β-treated CHON-001 cells. Moreover, miR-140-3p directly targeted MECP2, and upregulation of miR-140-3p attenuated L-1β-triggered CHON-001 cell injury via targeting MECP2. Additionally, circ_0136474 regulated MECP2 level via sponging miR-140-3p. CONCLUSION: Circ_0136474 knockdown alleviated IL-1β-triggered CHON-001 cell damage through modulation of miR-140-3p/MECP2 axis, indicating a new target for treatment of OA.
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