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长链非编码RNA PVT1通过作为miR-488-3p的海绵来调节骨关节炎中的软骨细胞凋亡。

LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a Sponge for miR-488-3p.

作者信息

Li Yufei, Li Shuhua, Luo Yatong, Liu Yong, Yu Nanhui

机构信息

1 Department of Surgery, Medical College, Hunan Normal University , Changsha, China .

2 Department of Pharmacy, Changsha Maternal and Child Health Hospital , Changsha, China .

出版信息

DNA Cell Biol. 2017 Jul;36(7):571-580. doi: 10.1089/dna.2017.3678. Epub 2017 May 18.

Abstract

Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse diseases, including osteoarthritis (OA). The present study aims at exploring the biological role of lncRNA plasmacytoma variant translocation 1 (PVT1) in OA and the underlying mechanism. Results showed that the expression of PVT1 was upregulated in OA chondrocytes compared with normal chondrocytes, silencing PVT1 inhibited the apoptosis of OA chondrocytes, and overexpression of PVT1 promoted the apoptosis of normal chondrocytes. To further investigate the underlying mechanism, miR-488-3p was predicted to be a targeted microRNA of PVT1. Different methods, including MS2 RNA immunoprecipitation (RIP), luciferase activity, and anti-AGO2 RIP, were performed to detect the interaction between PVT1 and miR-488-3p, which suggested that PVT1 negatively regulated miR-488-3p in OA chondrocytes. Moreover, PVT1 promoted the apoptosis of OA and normal chondrocytes through miR-488-3p. Collectively, this study revealed that lncRNA PVT1 regulated the apoptosis of chondrocytes by acting as a sponge for miR-488-3p in OA. PVT1 may be considered a new therapeutic target for the treatment of OA.

摘要

已知长链非编码RNA(lncRNA)参与多种不同疾病,包括骨关节炎(OA)。本研究旨在探讨lncRNA浆细胞瘤变异易位1(PVT1)在OA中的生物学作用及其潜在机制。结果显示,与正常软骨细胞相比,OA软骨细胞中PVT1的表达上调,沉默PVT1可抑制OA软骨细胞凋亡,而PVT1过表达则促进正常软骨细胞凋亡。为进一步研究潜在机制,预测miR-488-3p是PVT1的靶向微小RNA。采用包括MS2 RNA免疫沉淀(RIP)、荧光素酶活性和抗AGO2 RIP在内的不同方法检测PVT1与miR-488-3p之间的相互作用,结果表明PVT1在OA软骨细胞中对miR-488-3p起负调控作用。此外,PVT1通过miR-488-3p促进OA软骨细胞和正常软骨细胞凋亡。总体而言,本研究揭示lncRNA PVT1在OA中通过充当miR-488-3p的海绵来调节软骨细胞凋亡。PVT1可能被视为治疗OA的新治疗靶点。

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