Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 128, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.110349
Keywords
LncRNA XIST; Osteoarthritis; miR-149-5p; DNMT3A
Funding
- Scientific and Technological Research Project of Henan Province [141PPTGG295]
- Natural Project of The Department of Science and Technology of Henan Province [182300410349]
- Joint Construction Project of The Health and Health Commission of Henan Province [201701017]
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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-1 beta-treated chondrocytes. XIST knockdown promoted cell viability but restrained cell apoptosis and extracellular matrix (ECM) protein degradation in IL-1 beta-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.
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