Qin Chong-Zhen, Lv Qiao-Li, Yang Yan-Tao, Zhang Jing-Min, Zhang Xiao-Jian, Zhou Hong-Hao
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Chem Biol Drug Des. 2017 May;89(5):806-814. doi: 10.1111/cbdd.12906. Epub 2016 Dec 5.
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.
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。