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A172 胶质母细胞瘤细胞的化疗耐药性受 miR-1271 调控的 Bcl-2 控制。

Chemo-resistance of A172 glioblastoma cells is controlled by miR-1271-regulated Bcl-2.

机构信息

Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen, 518110, China.

Department of Pharmacology and Toxicology, Wright State University, Fairbon, OH 45435, USA.

出版信息

Biomed Pharmacother. 2018 Dec;108:734-740. doi: 10.1016/j.biopha.2018.08.102. Epub 2018 Sep 21.

DOI:10.1016/j.biopha.2018.08.102
PMID:30248541
Abstract

MicroRNAs (miRNAs) have been reported to exert important effects on the initiation, progression and metastasis of glioblastoma multiforme (GBM). In this study, we aimed to explore the regulation role of miR-1271 on the development of GBM. We found that miR-1271 was a Bcl-2-targeting miRNA, and the levels of miR-1271was decreased in samples from patients with GBM, compared with those from corresponding normal tissue samples. On the other hand, the levels of miR-1271 were inversely related to the levels of Bcl-2, which have been significantly increased in GBM samples. The overall survival was poorer in patients with low levels of miR-1271, compared to those with high levels of miR-1271. In vitro, the chemo-resistant cell survival mediated with Bcl-2 was inhibited by overexpression of miR-1271 and was enhanced by depletion of miR-1271. Thus, the chemo-resistance of GBM cells may be promoted after suppressing miR-1271 through cell survival mediated with Bcl-2. The prognosis of patients with GBM receiving chemotherapy may be improved by overexpressing miR-1271 in cancerous cells.

摘要

微小 RNA(miRNA)已被报道对胶质母细胞瘤(GBM)的发生、发展和转移有重要影响。在本研究中,我们旨在探索 miR-1271 对 GBM 发展的调控作用。我们发现 miR-1271 是 Bcl-2 的靶向 miRNA,与相应的正常组织样本相比,GBM 患者样本中的 miR-1271 水平降低。另一方面,miR-1271 的水平与 Bcl-2 的水平呈负相关,而 Bcl-2 在 GBM 样本中显著增加。与 miR-1271 水平高的患者相比,miR-1271 水平低的患者总体生存率较差。在体外,通过过表达 miR-1271 抑制 Bcl-2 介导的耐化疗细胞存活,而通过耗尽 miR-1271 增强 Bcl-2 介导的耐化疗细胞存活。因此,通过 Bcl-2 介导的细胞存活抑制 miR-1271 可能会促进 GBM 细胞的化疗耐药性。在癌细胞中过表达 miR-1271 可能会改善接受化疗的 GBM 患者的预后。

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