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miR-222-3p 靶向 CDKN1B 可能有助于椎间盘退行性变的发生。

Targeting of CDKN1B by miR-222-3p may contribute to the development of intervertebral disc degeneration.

机构信息

Department of Osteology The Third Affiliated Hospital of Guangxi Medical University Nanning China.

Department of Spine Osteopathia The First Affiliated Hospital of Guangxi Medical University Nanning China.

出版信息

FEBS Open Bio. 2019 Mar 12;9(4):728-735. doi: 10.1002/2211-5463.12609. eCollection 2019 Apr.

Abstract

MicroRNAs (miRNAs) are small endogenous non-coding RNAs that can negatively regulate the expression of their complementary mRNA targets, and have been implicated in various pathophysiological processes. In this study, we examined the effect of miR-222-3p on intervertebral disc degeneration (IDD). We found that expression of miR-222-3p was significantly higher in IDD tissues than in normal intervertebral disc tissue, and report that overexpression of miR-222-3p remarkably increased apoptosis and reduced proliferation of nucleus pulposus (NP) cells. In addition, miR-222-3p promoted secretion of matrix metalloproteinase-3, and decreased collagen type II and aggrecan production. Cyclin-dependent kinase inhibitor 1B (CDKN1B) was identified as a direct target of negative regulation by miR-222-3p in NP cells, and expression of miR-222-3p was found to be negatively correlated with that of CDKN1B in IDD tissue. Finally, we observed that transfection with miR-222-3p dramatically reduced CDKN1B expression in NP cells. In conclusion, miR-222-3p may be involved in IDD development, possibly through targeting CDKN1B.

摘要

微小 RNA(miRNAs)是小型内源性非编码 RNA,可以负调控与其互补的 mRNA 靶标,与多种病理生理过程有关。本研究探讨了 miR-222-3p 对椎间盘退变(IDD)的影响。结果发现,miR-222-3p 在 IDD 组织中的表达显著高于正常椎间盘组织,并报道 miR-222-3p 的过表达显著增加了核髓核(NP)细胞的凋亡,减少了增殖。此外,miR-222-3p 促进了基质金属蛋白酶-3 的分泌,降低了Ⅱ型胶原和聚集蛋白聚糖的产生。细胞周期蛋白依赖性激酶抑制剂 1B(CDKN1B)被鉴定为 NP 细胞中 miR-222-3p 负调控的直接靶标,miR-222-3p 的表达与 IDD 组织中 CDKN1B 的表达呈负相关。最后,我们观察到转染 miR-222-3p 可显著降低 NP 细胞中 CDKN1B 的表达。综上所述,miR-222-3p 可能通过靶向 CDKN1B 参与 IDD 的发生发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/156c/6443998/9c0b859977b2/FEB4-9-728-g001.jpg

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