miR-133 is a key negative regulator of CDC42-PAK pathway in gastric cancer
miR-133 is a key negative regulator of CDC42-PAK pathway in gastric cancer
复制标题
miR-133是胃癌CDC42-PAK通路的关键负调节因子
DOI：
10.1016/j.cellsig.2014.08.012
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发表时间：
2014-12-01
影响因子：
4.8
通讯作者：
Li, Feng
中科院分区：
文献类型：
--
作者：
Cheng, Zhenguo;Liu, Funan;Li, Feng
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.
