MicroRNA-125a-5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression

被引:44
作者
Cao, Yi [1 ]
Tan, Shengxing [1 ]
Tu, Yi [2 ]
Zhang, Guoyang [1 ]
Liu, Yi [1 ]
Li, Daojiang [1 ]
Xu, Shan [2 ]
Le, Zhibiao [1 ]
Xiong, Jianbo [1 ]
Zou, Wenyu [1 ]
Gong, Peitao [1 ]
Li, Zhengrong [1 ]
Jie, Zhigang [1 ]
机构
[1] Nanchang Univ, Affiliated Hosp 1, Dept Gen Surg, 17 Yongwai Zheng Rd, Nanchang 330006, Jiangxi, Peoples R China
[2] Nanchang Univ, Affiliated Hosp 1, Dept Pathol, Nanchang 330006, Jiangxi, Peoples R China
基金
美国国家科学基金会;
关键词
microRNA-125a-5p; breast cancer metastasis suppressor 1; gastric cancer; Invasion and metastasis; EPITHELIAL-MESENCHYMAL TRANSITION; MICRORNAS; PROLIFERATION; APOPTOSIS; CONTRIBUTES; MIR-125A-5P; SUPPRESSOR; PROFILES; FAMILY;
D O I
10.3892/ol.2018.7983
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Accumulating studies have demonstrated microRNAs (miRNAs/miRs) have an important role in multiple processes of human malignant tumor development and progression. Decreased expression of miR-125a-5p has been observed in several types of cancer, including gastric cancer (GC). However, the mechanism and exact function of miR-125a-5p in GC have not been largely elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction indicated that the expression of miR-125a-5p was downregulated in GC tissues and cell lines compared with matched normal tissues (P<0.01) and normal gastric mucosa cell lines (P<0.01), respectively. Moreover, clinical pathological characteristics and Kaplan-Meier analysis indicated that a low expression of miR-125a-5p was not only associated with lymph metastasis, peritoneal dissemination and advanced tumor-node metastasis stage but also affected the prognosis of GC patients. Compared with miR-control-transfected GC cells, markedly decreased migration and invasion was observed in GC cells that overexpress miR-125a-5p. By contrast, increased metastasis and invasion were observed in miR-125a-5p-knocked down cells compared with the control. Furthermore, luciferase reporter assays indicated that breast cancer metastasis suppressor 1 (BRMS1) was a direct target of miR-125a-5p. Notably, a positive correlation between the levels of BRMS1 and miR-125a-5p in GC tissues was observed, and BRMS1 expression was indicated to be regulated by miR-125a-5p in GC cells. In conclusion, miR-125a-5p may act as a tumor suppressor by targeting the metastasis-inhibitory gene, BRMS1. The data suggesting that BRMS1 is a potential target gene of miR-125a-5p, may provide novel insight into miRNA regulation of human gene expression, and a useful target for gene therapy of GC.
引用
收藏
页码:5119 / 5130
页数:12
相关论文
共 43 条
[1]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer [J].
Chen, Dong-liang ;
Zhang, Dong-sheng ;
Lu, Yun-xin ;
Chen, Le-zong ;
Zeng, Zhao-lei ;
He, Ming-ming ;
Wang, Feng-hua ;
Li, Yu-hong ;
Zhang, Hui-zhong ;
Pelicano, Helene ;
Zhang, Wei ;
Xu, Rui-hua .
ONCOTARGET, 2015, 6 (13) :10868-10879
[4]   MicroRNA Association with Synucleinopathy Conversion in Rapid Eye Movement Behavior Disorder [J].
Fernandez-Santiago, Ruben ;
Iranzo, Alex ;
Gaig, Carles ;
Serradell, Monica ;
Fernandez, Manel ;
Tolosa, Eduardo ;
Santamaria, Joan ;
Ezquerra, Mario .
ANNALS OF NEUROLOGY, 2015, 77 (05) :895-901
[5]   microRNAs: Master Regulators as Potential Therapeutics in Cancer [J].
Garofalo, Michela ;
Croce, Carlo M. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 51, 2011, 2011, 51 :25-43
[6]   Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer [J].
Gong, Jianan ;
Li, Jianxiong ;
Wang, Yi ;
Liu, Changzheng ;
Jia, Hongyan ;
Jiang, Chongliang ;
Wang, Yuxuan ;
Luo, Min ;
Zhao, Hongmei ;
Dong, Lei ;
Song, Wei ;
Wang, Fang ;
Wang, Weibin ;
Zhang, Junwu ;
Yu, Jia .
CARCINOGENESIS, 2014, 35 (02) :497-506
[7]   MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1 [J].
Han, Tae-Su ;
Hur, Keun ;
Xu, Guorong ;
Choi, Boram ;
Okugawa, Yoshinaga ;
Toiyama, Yuji ;
Oshima, Hiroko ;
Oshima, Masanobu ;
Lee, Hyuk-Joon ;
Kim, V. Narry ;
Chang, Aaron N. ;
Goel, Ajay ;
Yang, Han-Kwang .
GUT, 2015, 64 (02) :203-U30
[8]   Gastric cancer [J].
Hartgrink, Henk H. ;
Jansen, Edwin P. M. ;
van Grieken, Nicole C. T. ;
van de Velde, Cornelis J. H. .
LANCET, 2009, 374 (9688) :477-490
[9]   miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis [J].
Hsieh, Tsung-Hua ;
Hsu, Chia-Yi ;
Tsai, Cheng-Fang ;
Long, Cheng-Yu ;
Chai, Chee-Yin ;
Hou, Ming-Feng ;
Lee, Jau-Nan ;
Wu, Deng-Chyang ;
Wang, Shao-Chun ;
Tsai, Eing-Mei .
ONCOTARGET, 2015, 6 (01) :494-509
[10]   Metastasis suppression by BRMS1 associated with SIN3 chromatin remodeling complexes [J].
Hurst, Douglas R. .
CANCER AND METASTASIS REVIEWS, 2012, 31 (3-4) :641-651