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miR-29a-5p 通过靶向DHRS4调控胶质瘤的增殖、侵袭和迁移。

miR-29a-5p Regulates the Proliferation, Invasion, and Migration of Gliomas by Targeting DHRS4.

作者信息

Dai Yong, Chen Zhenhua, Zhao Wei, Cai Gang, Wang Zhifeng, Wang Xuejiang, Hu Hongkang, Zhang Yi

机构信息

Department of Neurosurgery, Second Affiliated Hospital of Nantong University, Nantong, China.

Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Front Oncol. 2020 Sep 10;10:1772. doi: 10.3389/fonc.2020.01772. eCollection 2020.

Abstract

Gliomas are the most common malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotypes. MicroRNAs (miRNAs) play a regulatory role in various cancers, including gliomas; however, their specific roles and mechanisms have not been fully investigated. Studies have indicated that miR-29a is a tumor-suppressive miRNA, but the data are limited. In this study, we investigated the role of miR-29a-5p in glioma and further explored its underlying mechanisms. On the basis of bioinformatics, dehydrogenase/reductase 4 (DHRS4) was considered a potential target of miR-29a-5p and was also found to be highly expressed in gliomas in our experiments. Moreover, with a luciferase reporter assay, DHRS4 was found to be a target gene of miR-29a-5p and to be correlated with glioma proliferation, invasion, and migration in our and experiments. Simultaneously, we observed that the knockdown of DHRS4 rescued the downregulation of glioma proliferation, invasion, and migration caused by treatment with a mir-29a-5p inhibitor. The present findings demonstrate that miR-29a-5p suppresses cell proliferation, invasion, and migration by targeting DHRS4, and DHRS4 may be a potential new oncogene and prognostic factor in gliomas.

摘要

神经胶质瘤是成人中最常见的原发性恶性脑肿瘤,并表现出一系列异常侵袭性表型。微小RNA(miRNA)在包括神经胶质瘤在内的各种癌症中发挥调节作用;然而,它们的具体作用和机制尚未得到充分研究。研究表明,miR-29a是一种肿瘤抑制性miRNA,但相关数据有限。在本研究中,我们研究了miR-29a-5p在神经胶质瘤中的作用,并进一步探讨了其潜在机制。基于生物信息学,脱氢酶/还原酶4(DHRS4)被认为是miR-29a-5p的潜在靶点,并且在我们的实验中也发现其在神经胶质瘤中高表达。此外,通过荧光素酶报告基因检测,我们发现DHRS4是miR-29a-5p的靶基因,并且在我们的实验中与神经胶质瘤的增殖、侵袭和迁移相关。同时,我们观察到敲低DHRS4可挽救由mir-29a-5p抑制剂处理导致的神经胶质瘤增殖、侵袭和迁移的下调。本研究结果表明,miR-29a-5p通过靶向DHRS4抑制细胞增殖、侵袭和迁移,并且DHRS4可能是神经胶质瘤中一种潜在的新癌基因和预后因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b346/7511594/bec3ada14cba/fonc-10-01772-g001.jpg

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