miR-206 functions as a novel cell cycle regulator and tumor suppressor in clear-cell renal cell carcinoma
miR-206 functions as a novel cell cycle regulator and tumor suppressor in clear-cell renal cell carcinoma
复制标题
miR-206 在透明细胞肾细胞癌中充当新型细胞周期调节剂和肿瘤抑制因子。
DOI：
10.1016/j.canlet.2016.01.032
复制
发表时间：
2016-04-28
期刊：
影响因子：
9.7
通讯作者：
Xu, Hua
中科院分区：
文献类型：
--
作者：
Xiao, Haibing;Xiao, Wei;Xu, Hua
目的：本研究旨在系统研究ccRCC中的抑瘤microRNA。材料与方法：采用MTS细胞存活率和集落形成实验，系统检测ccRCC中下调miRNAs的抑瘤能力。采用RT-qPCR和原位杂交检测miR-206在ccRCC细胞系和临床标本中的表达。寡核苷酸用于过表达或下调miR-206。进行MTS细胞活力、EdU细胞增殖、集落形成测定、流式细胞术、皮下异种移植和原位移植以检查miR-206在体外和体内的肿瘤抑制作用。结果：通过对已有的ccRCC组织中miRNA表达谱数据的分析，确定miR-206是ccRCC中最关键的抑瘤microRNA之一。结论：miR-206在肾细胞癌中具有细胞周期调控和抑癌作用，可作为肾细胞癌治疗的潜在靶点。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Purpose: In this study we tried to systematically investigate the tumor suppressing microRNAs in ccRCC.Materials and methods: The MTS cell viability and colony formation assay were used to systematically detect the tumor suppressing ability of down-regulated miRNAs in ccRCC. Then miR-206 expression was detected by RT-qPCR and in situ hybridization in ccRCC cell lines and clinical samples. Oligonucleotides were used to overexpress or down-regulate miR-206. MTS cell viability, EdU cell proliferation, colony formation assay, flow cytometry, Xenograft subcutaneously and orthotopic implantations were done to examine tumor suppressing effects of miR-206 in vitro and in vivo. Luciferase assay was performed to verify the precise target of miR-206.Results: We reviewed and experimentally analyzed the currently available miRNA expression profiles data of ccRCC and identified miR-206 as one of the most critical tumor-suppressing microRNAs in ccRCC. In addition, miR-206 inhibited ccRCC cell proliferation through inducing cell cycle arrest by directly targeting cell cycle related gene CDK4, CDK9 and CCNDI.Conclusions: All these results suggested that miR-206 functioned as a novel cell cycle regulator and tumor suppressor in ccRCC and could be considered as a potential target for ccRCC therapy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.