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PCGEM1 通过充当 miR-770 的海绵来刺激骨关节炎滑膜细胞的增殖。

PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770.

作者信息

Kang Yeonho, Song Jinsoo, Kim Dongkyun, Ahn Chiyeon, Park Sujung, Chun Churl-Hong, Jin Eun-Jung

机构信息

Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea.

Department of Orthopedic Surgery, Wonkwang University School of Medicine, Iksan, Chunbuk, 570-749, Korea.

出版信息

J Orthop Res. 2016 Mar;34(3):412-8. doi: 10.1002/jor.23046. Epub 2015 Sep 21.

Abstract

Long non-coding RNAs (lncRNAs) have been reported to play important roles in cellular metabolism and development. Various diseases have been associated with aberrant expression of lncRNAs and the related dysregulation of mRNAs. An lncRNA profiling assay was carried out to identify the key lncRNA in osteoarthritic human synoviocytes; the results revealed that prostate cancer gene expression marker 1 (PCGEM1) was significantly overexpressed in osteoarthritic synoviocytes. Exogenous overexpression of PCGEM1 inhibited apoptosis, induced autophagy, and stimulated the proliferation of human synoviocytes. The increased expression of PCGEM1 in human synoviocytes also suppressed the expression of miR-770. Transfection of the miR-770 precursor resulted in reduced proliferation, and induced apoptosis of human synoviocytes. This effect of miR-770 expression was reversed by co-introduction of PCGEM1. Target validation showed a direct binding between PCGEM1 and miR-770. We demonstrate that PCGEM1 act as sponge lncRNA for miR-770 that regulates proliferation/apoptosis and autophagy, and suggest PCGEM1 as possible target for OA therapy.

摘要

据报道,长链非编码RNA(lncRNA)在细胞代谢和发育中发挥重要作用。多种疾病与lncRNA的异常表达及相关mRNA的失调有关。开展了一项lncRNA谱分析试验,以鉴定骨关节炎人类滑膜细胞中的关键lncRNA;结果显示,前列腺癌基因表达标志物1(PCGEM1)在骨关节炎滑膜细胞中显著过表达。PCGEM1的外源性过表达抑制了细胞凋亡,诱导了自噬,并刺激了人类滑膜细胞的增殖。PCGEM1在人类滑膜细胞中表达增加还抑制了miR-770的表达。转染miR-770前体导致人类滑膜细胞增殖减少并诱导其凋亡。共导入PCGEM1可逆转miR-770表达的这种效应。靶点验证显示PCGEM1与miR-770之间存在直接结合。我们证明PCGEM1作为miR-770的海绵lncRNA调节增殖/凋亡和自噬,并提示PCGEM1可能是骨关节炎治疗的靶点。

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