MicroRNA-186 suppresses cell proliferation and metastasis through targeting MAP3K2 in non-small cell lung cancer

被引:54
作者
Huang, Tonghai [1 ,3 ,4 ]
She, Kelin [1 ,3 ]
Peng, Guilin [2 ]
Wang, Wei [2 ]
Huang, Jun [2 ]
Li, Jingpei [2 ]
Wang, Zheng [4 ]
He, Jianxing [1 ,2 ,3 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Guangzhou 510515, Guangdong, Peoples R China
[2] Guangzhou Med Univ, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis, State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China
[3] Guangzhou Med Univ, Affiliated Hosp 1, Dept Thorac Surg, 151 Yanjiang Rd, Guangzhou 510120, Guangdong, Peoples R China
[4] Shenzhen Peoples Hosp, Dept Thorac Surg, Shenzhen 518020, Guangdong, Peoples R China
关键词
non-small cell lung cancer; miRNA-186; growth; metastasis; apoptosis; MAP3K2; GENE-EXPRESSION; DOWN-REGULATION; ACTIVATION; BIOGENESIS; KINASE; GROWTH; MEKK2;
D O I
10.3892/ijo.2016.3637
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs are a class of small endogenous non coding RNAs that play crucial roles in the initiation and progression of human cancers. miR-186 was found decreased in various human malignancies and function as a tumor suppressor. However, the regulating mechanism of miR-186 in growth and metastasis of human non-small cell lung cancer (NSCLC) is still poorly understood. We investigated the role of miR-186 in the growth and metastasis of human NSCLC. In the present study, we found that miR-186 was significantly decreased in lung cancer tissues and cells. Furthermore, overexpression of miR-186 suppressed lung cancer cell proliferation, migration and invasion, and induced cell apoptosis. Moreover, we found that confirmed mitogen-activated protein kinase kinase kinase 2 (MAP3K2) protein was increased in lung cancer tissues and confirmed that MAP3K2 is a target gene of miR-186. In addition, knockdown of MAP3K2 by RNA interference inhibited lung cancer cell proliferation, migration and invasion, and promoted cell apoptosis in vitro. Furthermore, we observed tthat the overexpression of MAP3K2 partially reversed the inhibitory effect of miR-186 on the proliferation and metastasis of A549 and HCC827 cell lines. Taken together; our data indicated that miR-186 regulates lung cancer growth and metastasis through suppressing MAP3K2 expression, at least partly. Therefore, miR-186-MAP3K2 may represent a new and useful potential clinical treatment and diagnosis target for NSCLC.
引用
收藏
页码:1437 / 1444
页数:8
相关论文
共 36 条
[1]   Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs [J].
Bartel, DP ;
Chen, CZ .
NATURE REVIEWS GENETICS, 2004, 5 (05) :396-400
[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]   bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila [J].
Brennecke, J ;
Hipfner, DR ;
Stark, A ;
Russell, RB ;
Cohen, SM .
CELL, 2003, 113 (01) :25-36
[4]   miR-186 Downregulation Correlates with Poor Survival in Lung Adenocarcinoma, Where It Interferes with Cell-Cycle Regulation [J].
Cai, Junchao ;
Wu, Jueheng ;
Zhang, Huizhong ;
Fang, Lishan ;
Huang, Yongbo ;
Yang, Yi ;
Zhu, Xun ;
Li, Rong ;
Li, Mengfeng .
CANCER RESEARCH, 2013, 73 (02) :756-766
[5]   Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue [J].
Cazares, Lisa H. ;
Troyer, Dean ;
Mendrinos, Sawas ;
Lance, Raymond A. ;
Nyalwidhe, Julius O. ;
Beydoun, Hind A. ;
Clements, Mary Ann ;
Drake, Richard R. ;
Semmes, O. John .
CLINICAL CANCER RESEARCH, 2009, 15 (17) :5541-5551
[6]   Role of MEKK2-MEK5 in the regulation of TNF-α gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells [J].
Chayama, K ;
Papst, PJ ;
Garrington, TP ;
Pratt, JC ;
Ishizuka, T ;
Webb, S ;
Ganiatsas, S ;
Zon, LI ;
Sun, WY ;
Johnson, GL ;
Gelfand, EW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (08) :4599-4604
[7]   MicroRNAs modulate hematopoietic lineage differentiation [J].
Chen, CZ ;
Li, L ;
Lodish, HF ;
Bartel, DP .
SCIENCE, 2004, 303 (5654) :83-86
[8]   Systemic review of the patterns of failure following stereotactic body radiation therapy in early-stage non-small-cell lung cancer: Clinical implications [J].
Chi, Alexander ;
Liao, Zhongxing ;
Nguyen, Nam P. ;
Xu, Jiahong ;
Stea, Baldassarre ;
Komaki, Ritsuko .
RADIOTHERAPY AND ONCOLOGY, 2010, 94 (01) :1-11
[9]   MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells [J].
Cui, Guanghui ;
Cui, Mingwei ;
Li, Yuhang ;
Liang, Youguang ;
Li, Weihao ;
Guo, Haizhou ;
Zhao, Song .
TUMOR BIOLOGY, 2014, 35 (09) :8933-8937
[10]   Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs [J].
Erdmann, Kati ;
Kaulke, Knut ;
Thomae, Cathleen ;
Huebner, Doreen ;
Sergon, Mildred ;
Froehner, Michael ;
Wirth, Manfred P. ;
Fuessel, Susanne .
BMC CANCER, 2014, 14