Positive feedback loop of lncRNA FAM201A/miR‑146a‑5p/POU2F1 regulates IL‑1β‑induced chondrocyte injury invitro.

Abstract

Numerous studies have previously demonstrated that long non-coding RNAs (lncRNAs) serve an important regulatory role in osteoarthritis (OA). In particular, the lncRNA family with sequence similarity 201 member A (FAM201A) was previously found to be downregulated in necrotic femoral head samples. However, the role of FAM201A in IL-1β-induced chondrocyte injury remains unclear. It was hypothesized that FAM201A may exert a protective effect on IL-1β-induced chondrocyte injury in OA by sponging microRNAs (miRNAs/miRs). The purpose of the present study was to explore the role and molecular mechanism of FAM201A in IL-1β-induced chondrocyte injury. A model of OA was established by stimulation C-28/I2 cell with IL-1β in vitro. The expression levels of FAM201A following IL-1β-induced chondrocyte injury were detected via reverse transcription-quantitative PCR. Luciferase reporter assay was used to assess the possible associations among FAM201A, miR-146a-5p and POU class 2 homeobox 1 (POU2F1). Chromatin immunoprecipitation assay was performed to analyze the interaction between POU2F1 and miR-146a-5p. ELISA, TUNEL and western blotting were performed to measure the level of inflammation, lactate dehydrogenase release, apoptosis and the expression of apoptosis-related proteins (Bcl-2, Bax, cleaved caspase 3 and cleaved caspase 9), respectively. The expression levels of FAM201A were found to be downregulated following IL-1β-induced chondrocyte injury. Overexpression of FAM201A exerted a protective effect against IL-1β-induced chondrocyte injury. In addition, FAM201A could upregulate the expression levels of POU2F1 by sponging miR-146a-5p. Further experiments revealed that POU2F1 could bind to the promoter region of FAM201A and subsequently regulate the expression levels of POU2F1, indicating a role for the FAM201A/miR-146a-5p/POU2F1 positive feedback loop in IL-1β-induced chondrocyte injury. The present study revealed the protective effects of the FAM201A/miR-146a-5p/POU2F1 positive feedback loop on IL-1β-induced chondrocyte injury and provided a potential therapeutic target for OA.