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  • Title: LncRNA MALAT1 mediates proliferation of LPS treated-articular chondrocytes by targeting the miR-146a-PI3K/Akt/mTOR axis.
    Author: Li H, Xie S, Li H, Zhang R, Zhang H.
    Journal: Life Sci; 2020 Aug 01; 254():116801. PubMed ID: 31472145.
    Abstract:
    The study aimed to investigate the regulation of long noncoding RNA (lncRNA), Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in osteoarthritis (OA) development. Isolated rat chondrocytes treated with lipopolysaccharide (LPS) were used as OA cell model. Results from quantitative real-time PCR (Q-PCR) showed that, in OA patients and OA cell model, the expression of MALAT1 and PI3K was clearly reduced, while the miR-146a levels were increased. Next, MALAT1 was silenced in LPS-treated chondrocytes. Following with MALAT1 silencing, the generation of Cyclooxygenase-2 (COX-2), Interleukin-6 (IL-6) and Matrix metallopeptidase-13 (MMP-13) were promoted, while the level of type II collagen (COL2) was inhibited. Moreover, MALAT1 silencing caused a significant reduction in the proliferative rate of LPS-treated chondrocytes through inducing apoptosis. Bioinformatics prediction and dual-luciferase reporter assay (DLRA) results showed that MALAT1 targets miR-146a. MALAT1 silencing also resulted in the upregulation of miR-146a. Further studies revealed that miR-146a has the opposite effect on MALAT1, and its inhibition can antagonize the function of MALAT1 silencing on cell proliferation and apoptosis. Additionally, the 3'-UTR of the Phosphoinositide 3-kinase (PI3K) gene was found to be a target of miR-146a, while PI3K protein and mRNA expression, as well as the activation of downstream Akt and mammalian target of rapamycin (mTOR) were clearly reduced upon transfection with a miR-146a mimic. These results show that MALAT1 can modulate ECM catabolism, inflammation, and especially apoptosis in chondrocytes treated with LPS, which targets PI3K/Akt/mTOR to eventually regulate the progression of OA. Our findings provide a novel regulatory mechanism of MALAT1 in OA.
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