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

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.

Exercise training attenuates angiotensin II-induced cardiac fibrosis by reducing POU2F1 expression

“…High-throughput sequencing revealed that POU2F1 is a target gene of microRNA-205-5p (miR-205-5p) and miR-146a-5p. 32 , 33 Another study revealed that the expressions of miR-205-5p and miR-146a-5p were increased by physical training. 34 Wang et al 35 found that exercise training could decrease the level of long noncoding RNA taurine upregulated gene 1.…”

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

“…CircRNA plays an important regulatory role in disease by interacting with disease‐associated microRNA and have also been shown to mediate chondrocyte apoptosis 72 . Due to the close relationships and similar effects among the above three, we list them as regulating chondrocyte apoptosis in Table 1 instead of showing them one by one 73–97 …”