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