MEG3 promotes proliferation and inhibits apoptosis in osteoarthritis chondrocytes by miR-361-5p/FOXO1 axis

Abstract

Background: This study aimed to investigate the role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) and related molecular mechanisms, in osteoarthritis (OA). Methods: Cartilage tissues of OA patients and healthy volunteers were isolated and cultured. After transfection with the appropriate constructs, chondrocytes were classified into Blank, pcDNA3.1-NC, pcDNA3.1-MEG3, si-NC, si-MEG3, pcDNA3.1-NC + mimics NC, pcDNA3.1-MEG3 + mimics NC, pcDNA3.1-NC + miR-361-5p mimics and pcDNA3.1-MEG3 + miR-361-5p mimics groups. qRT-PCR was used to detect the expression of MEG3, miR-361-5p and FOXO1. Western blot, luciferase reporter assay, RIP, CCK-8, and flow cytometry analysis were performed to reveal the morphology, proliferation, and apoptotic status of cartilage cells. Histological analysis and immunostaining were conducted in the OA rat model.Results: Expression of MEG3 and FOXO1 was significantly decreased in OA compared with the normal group, while the expression of miR-361-5p was increased. MEG3 might serve as a ceRNA of miR-361-5p in OA chondrocytes. Moreover, using western blot analyses and the CCK-8 assay, MEG3 was shown to target miR-361-5p/FOXO1, elevate cell proliferation, and impair cell apoptosis. Functional analysis in vivo showed that MEG3 suppressed degradation of the cartilage matrix. Conclusion: MEG3 can contribute to cell proliferation and inhibit cell apoptosis and degradation of extracellular matrix (ECM) via the miR-361-5p/FOXO1 axis in OA chondrocytes.

Comparative Analysis of the Glutathione S-Transferase Gene Family of Four Triticeae Species and Transcriptome Analysis of GST Genes in Common Wheat Responding to Salt Stress

“…The numbers of GST genes identified in these four species basically conform to their genome ploidy, which indicates that the GST gene family was conserved during the process of polyploidization. In a recent study, the GST gene family in common wheat was divided into eight classes [ 49 ], but there is evidence that the GST gene family also includes the OMEGA and MAPEG classes in plants [ 1 , 50 , 51 ]. To accurately identify the GST genes in common wheat and its relatives, we updated the classification of the GST genes and largely expanded the membership of this gene family.…”

The function of lncRNAs in the pathogenesis of osteoarthritis

“…It is a human homologue of mouse maternally imprinted gene trap locus 2 ( Glt2 ), which was first discovered by Miyoshi et al 123 in 2000. MEG3 has been reported in previous studies to reduce ECM degradation in OA chondrocytes, 43 , 44 and the interaction between MEG3 and SRY-associated high mobility protein-2 ( SOX2 ) induces the expression of BMP4 to promote osteogenic differentiation of bone marrow mesenchymal stem cells. 124 In addition, other studies have pointed out that overexpression of MEG3 leads to downregulation of the serine/threonine-specific protein kinase (known as protein kinase B (AKT)) signalling pathway in breast cancer, and the AKT signalling pathway plays a key role in the growth, invasion, and angiogenesis of breast cancer cells.…”

“…Chen et al 44 found that MEG3 , as a ceRNA of miR-93 , can promote the expression of transforming growth factor β receptor 2 ( TGFBR2 ), and then activate the TGF-β signalling pathway to reduce ECM degradation. In another study also aimed at MEG3 , Wang et al 43 found that MEG3 inhibits ECM degradation through the miR-361-5p/FOXO1 axis. The expression of MEG3 in human OA chondrocytes was downregulated, while overexpression of MEG3 significantly downregulated the expression of miR-93 and miR-361-5p , inhibiting the expression of MMP-13 and ADAMTS-5 which thus reduced degradation of the ECM.…”

“…The expression of MEG3 in human OA chondrocytes was downregulated, while overexpression of MEG3 significantly downregulated the expression of miR-93 and miR-361-5p , inhibiting the expression of MMP-13 and ADAMTS-5 which thus reduced degradation of the ECM. 43 …”

“…The above studies show that CIR is closely related to the occurrence and development of OA and can be used as a potential target for the treatment of OA. HOTAIR , 40 nuclear paraspeckle assembly transcript 1 ( NEAT1 ), 62 XIST , 50 and MEG3 43 , 44 also regulate not only the metabolism of ECM but also the apoptosis of chondrocytes. Several studies have shown that XIST can promote apoptosis in OA chondrocytes.…”