软骨细胞
小RNA
细胞凋亡
软骨
骨关节炎
下调和上调
化学
癌症研究
医学
基因
病理
生物化学
解剖
替代医学
作者
Yihui Tu,Tiancai Ma,Tao Wen,Tao Yang,Long Xue,Minwei Cai,Fangxin Wang,Mengying Guan,Hao Xue
标识
DOI:10.1016/j.bbrc.2019.11.186
摘要
Increasing evidence indicates that altered expression of microRNAs (miRNAs) is associated with osteoarthritis (OA) progression. In our study, we demonstrated that miR-377–3p is underexpressed in OA-affected cartilage and IL-1β–treated chondrocytes. Overexpression of miR-377–3p enhanced chondrocyte proliferation and restrained apoptosis and signs of cartilage matrix degradation and of an inflammatory response. Furthermore, ITGA6 was identified as a target gene of miR-377–3p. The latter was found to directly bind to the 3′ untranslated region (3′UTR) of ITGA6 mRNA and downregulate ITGA6. In addition, ITGA6 expression was high in OA-affected tissues and negatively correlated with miR-77–3p expression. Overexpression of ITGA6 reversed the effects of miR-377–3p on IL-1β–caused chondrocyte apoptosis, cartilage matrix degradation, and the inflammatory response. Moreover, bioinformatic analysis and a luciferase assay indicated that miR-377–3p expression is regulated by long noncoding RNA NEAT1, which binds to miR-377–3p and inactivates it. We showed that NEAT1 was highly expressed in OA-affected cartilage, negatively correlated with miR-377–3p levels, and positively correlated with ITGA6 levels. These findings provide information for the development of future treatments of OA, suggesting that miR-377–3p may be a therapeutic target in OA.
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