LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a Sponge for miR-488-3p
LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a Sponge for miR-488-3p
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DOI：
10.1089/dna.2017.3678
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发表时间：
2017-07-01
影响因子：
3.1
通讯作者：
Yu, Nanhui
中科院分区：
文献类型：
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作者：
Li, Yufei;Li, Shuhua;Yu, Nanhui
已知长链非编码RNA（lncRNA）与多种不同疾病有关，包括骨关节炎（OA）。本研究旨在探讨lncRNA浆细胞瘤变异易位1（PVT 1）在OA中的生物学作用及其机制。结果表明，与正常软骨细胞相比，PVT 1在OA软骨细胞中的表达上调，沉默PVT 1可抑制OA软骨细胞的凋亡，过表达PVT 1可促进正常软骨细胞的凋亡。为了进一步研究潜在的机制，miR-488- 3 p被预测为PVT 1的靶向microRNA。采用MS 2 RNA免疫沉淀法、荧光素酶法和抗AGO 2 RIP法检测PVT 1与miR-488- 3 p的相互作用，结果表明PVT 1对OA软骨细胞中miR-488- 3 p的表达具有负调控作用。PVT 1通过miR-488- 3 p促进OA和正常软骨细胞凋亡。总的来说，这项研究揭示了lncRNA PVT 1通过在OA中充当miR-488- 3 p的海绵来调节软骨细胞的凋亡。PVT 1可能被认为是治疗OA的新靶点。
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.