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微小 RNA-622 通过靶向 YAP1 抑制神经胶质瘤细胞的增殖。

MicroRNA-622 suppresses the proliferation of glioma cells by targeting YAP1.

机构信息

Department of Neurosurgery, The Firstiugiu Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Neurosurgery, Yancheng City No.1 People's Hospital, Yancheng, China.

出版信息

J Cell Biochem. 2018 Mar;119(3):2492-2500. doi: 10.1002/jcb.26343. Epub 2017 Dec 12.

Abstract

It has recently been shown that miR-622 plays a tumor suppressive role in many human cancers. However, the exact function and underlying mechanism are still unknown. Here, we reported that the level of miR-622 is clearly reduced in human glioma tissues in comparison with normal brain tissues and is negatively correlated with the histological grades. Additionally, ectopically expressed miR-622 significantly inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase in glioma cells. Furthermore, the bioinformatics analysis revealed that YAP1 possesses putative miR-622-binding sites within its 3'UTR. Consequently, an elevated miR-622 level was found to suppress the luciferase reporter activity of YAP1 3'UTR, and the effect was diminished by the deletion of the miR-622 seed binding site. In addition, the level of YAP1 protein expression was significantly decreased after the overexpression of miR-622. These results indicate a negative link between miR-622 and YAP1 and further confirm that YAP1 is a direct target of miR-622, suggesting that miR-622 could be a new important therapeutic strategy for gliomas treatment.

摘要

最近的研究表明,miR-622 在许多人类癌症中发挥肿瘤抑制作用。然而,其确切功能和潜在机制仍不清楚。在这里,我们报道 miR-622 在人胶质瘤组织中的水平明显低于正常脑组织,并且与组织学分级呈负相关。此外,外源性表达 miR-622 可显著抑制胶质瘤细胞的增殖,并诱导细胞周期停滞在 G0/G1 期。此外,生物信息学分析表明 YAP1 在其 3'UTR 内具有潜在的 miR-622 结合位点。因此,发现升高的 miR-622 水平可抑制 YAP1 3'UTR 的荧光素酶报告活性,并且该效应可通过缺失 miR-622 种子结合位点而减弱。此外,miR-622 过表达后 YAP1 蛋白表达水平显著降低。这些结果表明 miR-622 和 YAP1 之间存在负相关,进一步证实 YAP1 是 miR-622 的直接靶标,表明 miR-622 可能成为治疗胶质瘤的新的重要治疗策略。

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