miR-133 is a key negative regulator of CDC42-PAK pathway in gastric cancer

被引:47
作者
Cheng, Zhenguo [1 ,2 ]
Liu, Funan [3 ]
Wang, Guanqiao [1 ,2 ]
Li, Yanshu [1 ,2 ]
Zhang, Hongyan [1 ,2 ]
Li, Feng [1 ,2 ]
机构
[1] China Med Univ, Minist Publ Hlth, Dept Cell Biol, Key Lab Cell Biol, Shenyang 110001, Peoples R China
[2] China Med Univ, Minist Educ, Key Lab Med Cell Biol, Shenyang 110001, Peoples R China
[3] China Med Univ, Hosp 1, Dept Surg Oncol, Shenyang 110001, Peoples R China
基金
中国国家自然科学基金;
关键词
Gastric cancer; miR-133; p21-activated kinase; CDC42; Activation; Invasion; SMALL-MOLECULE INHIBITOR; DOWN-REGULATION; BREAST-CANCER; SUPPRESSES PROLIFERATION; RHO-GTPASES; EXPRESSION; KINASE; MICRORNAS; INVASION; TARGETS;
D O I
10.1016/j.cellsig.2014.08.012
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Cell division cycle 42 (CDC42), an important member of the Ras homolog (Rho) family, plays a key role in regulating multiple cellular processes such as cell cycle progression, migration, cell cytoskeleton organization, cell fate determination and differentiation. Among the downstream effectors of CDC42, P21-activated kinases (PAKs) obtain the most attention. Although a large body of evidence indicates that CDC42/PAKs pathway plays important role in tumor growth, invasion and metastasis, the mechanism of their negative regulation remains unclear. Here, we identified CDC42, a PAKs activating factor, was a target of miR-133. Ectopic overexpression of miRNAs not only downregulated CDC42 expression and PAKs activation, but also inhibited cancer cell proliferation and migration. We also found that miR-133 was down-regulated in 180 pairs gastric cancer tissues. miR-133 expression was negatively associated with tumor size, invasion depth and peripheral organ metastasis. Besides, dysfunction of miR-133 was an independent prognosis factor for overall survival. Our findings could provide new insights into the molecular mechanisms of gastric carcinogenesis, and may help facilitating development of CDC42/PAK-based therapies for human cancer. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:2667 / 2673
页数:7
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