MicroRNA-100 functions as a tumor suppressor by inhibiting Lgr5 expression in colon cancer cells

被引:45
作者
Zhou, Ming-Kai [1 ]
Liu, Xiao-Jun [1 ]
Zhao, Zhi-Guo [2 ]
Cheng, Yi-Meng [3 ]
机构
[1] Zhengzhou Univ, Intens Care Unit, Affiliated Hosp 2, Zhengzhou 450014, Henan, Peoples R China
[2] Zhengzhou Univ, Dept Gastroenterol, Affiliated Hosp 2, Zhengzhou 450014, Henan, Peoples R China
[3] Third Hosp Zhengzhou, Dept Neurol, Zhengzhou 450000, Henan, Peoples R China
关键词
colon cancer; microRNA; microRNA-100; G protein-coupled receptor 5; beta-catenin; COLORECTAL-CANCER; STEM-CELLS; HEPATOCELLULAR-CARCINOMA; SURVIVAL; MICE; WNT; PHOSPHATASE; PROGNOSIS; MARKER; GROWTH;
D O I
10.3892/mmr.2014.3052
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Previous studies have demonstrated that microRNAs (miRNAs), a class of single-stranded RNA molecules that are 18-27 nucleotides in length, serve a critical function in tumorigenesis, including in the development of colon cancer. In the current study, miR-100 levels were demonstrated to be reduced in colon cancer tissues compared with the levels in matched adjacent normal tissues. Forced overexpression of miR-100 by transfection with miR-100 mimics substantially inhibited the proliferation, migration and invasion of SW480 and HCT116 cells, whereas reduced expression, resulting from transfection of antisense oligonucleotides, promoted these processes. At the molecular level, miR-100 was observed to reduce the levels of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5), by binding to its 3-untranslated region. As a result of this, Wnt/-catenin signaling was affected by fluctuations in the level of miR-100 mimics or antisense. Collectively, the results of the current study elucidate a novel regulatory pathway involving miR-100 and Lgr5 in colon cancer cells, which may present a potential therapeutic target.
引用
收藏
页码:2947 / 2952
页数:6
相关论文
共 24 条
[1]
Diversifying microRNA sequence and function [J].
Ameres, Stefan L. ;
Zamore, Phillip D. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (08) :475-488
[2]
Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma [J].
Chen, Ping ;
Zhao, Xia ;
Ma, Liang .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2013, 383 (1-2) :49-58
[3]
Chiu BCH, 2003, CANCER EPIDEM BIOMAR, V12, P201
[4]
Des Guetz G, 2013, GASTROENT RES PRACT, V2013
[5]
Leucine-rich repeat-containing G protein-coupled receptor 5 regulates epithelial cell phenotype and survival of hepatocellular carcinoma cells [J].
Fukuma, Mariko ;
Tanese, Keiji ;
Effendi, Kathryn ;
Yamazaki, Ken ;
Masugi, Yohei ;
Suda, Mariko ;
Sakamoto, Michiie .
EXPERIMENTAL CELL RESEARCH, 2013, 319 (03) :113-121
[6]
miR-100 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling [J].
Gebeshuber, C. A. ;
Martinez, J. .
ONCOGENE, 2013, 32 (27) :3306-3310
[7]
Wnt Signaling, Lgr5, and Stem Cells in the Intestine and Skin [J].
Haegebarth, Andrea ;
Clevers, Hans .
AMERICAN JOURNAL OF PATHOLOGY, 2009, 174 (03) :715-721
[8]
MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61 [J].
Huang, Jianhua ;
Gao, Kanda ;
Lin, Jian ;
Wang, Qiugen .
TUMOR BIOLOGY, 2014, 35 (02) :1095-1100
[9]
The prognostic importance of miR-21 in stage II colon cancer: a population-based study [J].
Kjaer-Frifeldt, S. ;
Hansen, T. F. ;
Nielsen, B. S. ;
Joergensen, S. ;
Lindebjerg, J. ;
Soerensen, F. B. ;
Christensen, R. dePont ;
Jakobsen, A. .
BRITISH JOURNAL OF CANCER, 2012, 107 (07) :1169-1174
[10]
Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer [J].
Leushacke, M. ;
Barker, N. .
ONCOGENE, 2012, 31 (25) :3009-3022