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MicroRNA-138-5p 通过靶向 TRIP6 表达调控神经干细胞的增殖和分化。

MicroRNA‑138‑5p regulates neural stem cell proliferation and differentiation in vitro by targeting TRIP6 expression.

机构信息

Stem Cell Center, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.

Clinical Laboratory, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):7261-7266. doi: 10.3892/mmr.2017.7504. Epub 2017 Sep 18.

Abstract

Research on neural stem cells (NSCs) has recently focused on microRNAs (miRNAs), a class of small non‑coding RNAs that have crucial roles in regulating NSC proliferation and differentiation. In the present study, a quantitative‑polymerase chain reaction assay revealed that the expression of miRNA (miR)‑138‑5p was significantly decreased during neural differentiation of NSCs in vitro. Overexpression of miR‑138‑5p reduced NSC proliferation and increased NSC differentiation. Furthermore, suppression of miR‑138‑5p via transfection with a miRNA inhibitor enhanced NSC proliferation and attenuated NSC differentiation. Additionally, expression of thyroid hormone receptor interacting protein 6 (TRIP6), a critical regulator of NSCs, was negatively correlated with the miR‑138‑5p level. A luciferase assay demonstrated that miR‑138‑5p regulate TRIP6 by directly binding the 3'‑untranslated region of the mRNA. Additionally, upregulation of TRIP6 rescued the NSC proliferation deficiency induced by miR‑138‑5p and abolished miR‑138‑5p‑promoted NSCs differentiation. By contrast, downregulation of TRIP6 produced the opposite effect on proliferation and differentiation of NSCs transfected with anti‑miR‑138‑5p. Taken together, the data suggest that miR‑138‑5p regulates NSCs proliferation and differentiation, and may be useful in developing novel treatments for neurological disorders via manipulation of miR‑138‑5p in NSCs.

摘要

神经干细胞 (NSCs) 的研究最近集中在 microRNAs (miRNAs) 上,miRNAs 是一类小的非编码 RNA,在调节 NSCs 的增殖和分化方面发挥着关键作用。在本研究中,定量聚合酶链反应检测显示,miRNA (miR) -138-5p 的表达在 NSCs 的体外神经分化过程中显著降低。miR-138-5p 的过表达减少了 NSCs 的增殖并增加了 NSCs 的分化。此外,通过转染 miRNA 抑制剂抑制 miR-138-5p 增强了 NSCs 的增殖并减弱了 NSCs 的分化。此外,甲状腺激素受体相互作用蛋白 6 (TRIP6) 的表达与 miR-138-5p 水平呈负相关,TRIP6 是 NSCs 的关键调节因子。荧光素酶检测表明,miR-138-5p 通过直接结合 mRNA 的 3'非翻译区来调节 TRIP6。此外,TRIP6 的上调挽救了 miR-138-5p 诱导的 NSCs 增殖缺陷,并消除了 miR-138-5p 促进的 NSCs 分化。相比之下,下调 TRIP6 对转染抗 miR-138-5p 的 NSCs 的增殖和分化产生了相反的效果。综上所述,数据表明 miR-138-5p 调节 NSCs 的增殖和分化,并且通过操纵 NSCs 中的 miR-138-5p,可能有助于开发治疗神经障碍的新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5865854/d299c04b889e/mmr-16-05-7261-g00.jpg

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