Long non-coding RNA XIST contributes to osteoarthritis progression via miR-149-5p/DNMT3A axis - 18/06/20
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Graphical abstract |
LncRNA XIST leads to the proliferation inhibition, apoptosis acceleration and Collagen II/Aggrecan degradation in IL-1β-induced OA model by sponging miR-149-5p to increase DNMT3A.
Highlights |
• | XIST inhibits cell viability while promotes apoptosis and ECM degradation in OA. |
• | XIST targets miR-149-5p and DNMT3A is a downstream target of miR-149-5p. |
• | XIST downregulation reduces DNMT3A expression by elevating miR-149-5p. |
• | XIST silence impedes OA progression by affecting miR-149-5p/DNMT3A axis in vivo. |
Abstract |
Long non-coding RNAs (lncRNAs) are largely involved in the development of osteoarthritis (OA), a chronic and degenerative joint disease. The objective of this paper is to research the functional role and molecular mechanism of lncRNA X inactive specific transcript (XIST) in OA. The levels of XIST, microRNA-149-5p (miR-149-5p), and DNA methyltransferase 3A (DNMT3A) were measured. Cell viability and apoptosis rate were determined. Associated protein levels were examined through Western blot. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were implemented for confirming the target relation. And the role of XIST on OA in vivo was investigated by a rat model. XIST was expressed at a high level in OA cartilage tissues and IL-1β-treated chondrocytes. XIST knockdown promoted cell viability but restrained cell apoptosis and extracellular matrix (ECM) protein degradation in IL-1β-treated chondrocytes. XIST directly targeted miR-149-5p and miR-149-5p down-regulation restored si-XIST-mediated pro-proliferative and anti-apoptotic or ECM degradative effects. DNMT3A was a target gene of miR-149-5p and DNMT3A overexpression ameliorated miR-149-5p-induced promotion of cell viability but repression of apoptosis and ECM degradation. Knockdown of XIST reduced DNMT3A level by motivating miR-149-5p expression. The inhibitory influence of XIST down-regulation on OA evolvement was also achieved by miR-149-5p/DNMT3A axis in vivo. In a word, knockdown of XIST can repress the development of OA by miR-149-5p/DNMT3A axis. This study discovers the XIST/miR-149-5p/DNMT3A axis in regulating OA evolution, which is beneficial for understanding the molecular pathomechanism and can lay a good foundation for targeted therapy of OA treatment.
El texto completo de este artículo está disponible en PDF.Keywords : LncRNA XIST, Osteoarthritis, miR-149-5p, DNMT3A
Esquema
Vol 128
Artículo 110349- août 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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