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长链非编码 RNA SNHG1 通过调节 miR-326 和 CCND1 促进髓核细胞增殖。

The long noncoding RNA SNHG1 promotes nucleus pulposus cell proliferation through regulating miR-326 and CCND1.

机构信息

Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University , Zhengzhou , China.

出版信息

Am J Physiol Cell Physiol. 2018 Jul 1;315(1):C21-C27. doi: 10.1152/ajpcell.00220.2017. Epub 2018 Feb 21.

Abstract

Aberrant nucleus pulposus cell proliferation is implicated in the development of intervertebral disk degeneration (IDD). Recent studies have suggested that long noncoding RNAs (lncRNAs) can modulate cell proliferation in several pathological conditions. Here, we indicate that expression of SNHG1 was upregulated in IDD tissues compared with control tissues and that higher SNHG1 expression was associated with disk degeneration grade. In addition, we show that ectopic expression of SNHG1 promoted nucleus pulposus (NP) cell proliferation and increased the PCNA and cyclin D1 expression in NP cells. Ectopic expression of SNHG1 inhibited miR-326 expression in nucleus pulposus cells and promoted CCND1 expression, which is a direct target gene of SNHG1. Moreover, we demonstrate that expression of miR-326 was downregulated in IDD tissues compared with control tissues and that lower SNHG1 expression was associated with disk degeneration grade. Expression of miR-326 was negatively associated with SNHG1 expression in disk degeneration tissues. Overexpression of miR-326 inhibited NP cell growth and inhibited PCNA and cyclin D1 expression in NP cells. Furthermore, we show that overexpression of SNHG1 promoted nucleus pulposus cell proliferation through inhibiting miR-326 expression. These data shed novel light on the role of SNHG1 in the pathogenesis of IDD.

摘要

异常核髓核细胞增殖与椎间盘退行性变(IDD)的发生有关。最近的研究表明,长链非编码 RNA(lncRNAs)可以在几种病理条件下调节细胞增殖。在这里,我们表明 SNHG1 的表达在 IDD 组织中高于对照组织,并且 SNHG1 表达较高与椎间盘退变程度相关。此外,我们表明 SNHG1 的异位表达促进了核髓核(NP)细胞的增殖,并增加了 NP 细胞中的 PCNA 和细胞周期蛋白 D1 的表达。SNHG1 的异位表达抑制了核髓核细胞中 miR-326 的表达,并促进了 CCND1 的表达,这是 SNHG1 的直接靶基因。此外,我们证明 miR-326 的表达在 IDD 组织中低于对照组织,并且 SNHG1 表达较低与椎间盘退变程度相关。miR-326 的表达与椎间盘退变组织中的 SNHG1 表达呈负相关。miR-326 的过表达抑制了 NP 细胞的生长,并抑制了 NP 细胞中 PCNA 和细胞周期蛋白 D1 的表达。此外,我们表明,SNHG1 的过表达通过抑制 miR-326 的表达促进了核髓核细胞的增殖。这些数据为 SNHG1 在 IDD 发病机制中的作用提供了新的见解。

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