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微小RNA-320d的下调预示着胶质瘤患者总体生存率较低,并促进胶质瘤的生长和侵袭能力。

Downregulation of MicroRNA-320d predicts poor overall survival and promotes the growth and invasive abilities in glioma.

作者信息

Qin Chong-Zhen, Lv Qiao-Li, Yang Yan-Tao, Zhang Jing-Min, Zhang Xiao-Jian, Zhou Hong-Hao

机构信息

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Chem Biol Drug Des. 2017 May;89(5):806-814. doi: 10.1111/cbdd.12906. Epub 2016 Dec 5.

Abstract

Previous studies have demonstrated that miRNAs play an important role in tumor development and progression. The role of miR-320d has been studied in several cancers except for glioma. The aim of the study was to investigate the expression levels, biological function, and mechanism of miR-320d in glioma. The expression levels of miR-320d were detected in glioma tissues and cell lines (U87 and U251) by RT-qPCR. Cell proliferation, colony formation, apoptosis, cell cycle, and transwell assays were performed in glioma cell lines transfected with miR-320d mimics or controls to evaluate the effects of miR-320d in vitro. The expression levels of invasive-related proteins were determined by Western blot analysis. Results showed that the expression of miR-320d was significantly decreased in glioma tissues and cell lines. Overexpression of miR-320d could significantly suppress cell growth, migration and invasion, and induced cell apoptosis as well as cell cycle at G0/G1 arrest in U87 and U251 cell lines. Additionally, expression levels of MMP-2, MMP-9, N-cadherin, and integrin-β1 reduced, while E-cadherin increased in miR-320d mimic group. Overall, this study is the first to demonstrate that miR-320d may serve as an independent prognostic factor, indicating that miR-320d is a biomarker for prognosis and therapy in glioma.

摘要

先前的研究表明,微小RNA(miRNA)在肿瘤的发生和发展中起重要作用。除了神经胶质瘤外,miR-320d在几种癌症中的作用已得到研究。本研究的目的是探讨miR-320d在神经胶质瘤中的表达水平、生物学功能及机制。采用逆转录定量聚合酶链反应(RT-qPCR)检测神经胶质瘤组织和细胞系(U87和U251)中miR-320d的表达水平。用miR-320d模拟物或对照转染神经胶质瘤细胞系,进行细胞增殖、集落形成、凋亡、细胞周期及Transwell实验,以评估miR-320d在体外的作用。通过蛋白质免疫印迹分析确定侵袭相关蛋白的表达水平。结果显示,miR-320d在神经胶质瘤组织和细胞系中的表达显著降低。在U87和U251细胞系中,miR-320d的过表达可显著抑制细胞生长、迁移和侵袭,并诱导细胞凋亡以及使细胞周期停滞在G0/G1期。此外,在miR-320d模拟物组中,基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、N-钙黏蛋白和整合素-β1的表达水平降低,而E-钙黏蛋白的表达增加。总体而言,本研究首次证明miR-320d可能作为一个独立的预后因素,表明miR-320d是神经胶质瘤预后和治疗的一个生物标志物。

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