title: MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells.
abstract: MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3'UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.
authors: Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People's Hospital, Shanghai, PR China.
authors: Zhigang
authors: Z
authors: Wang
authors: Xiaoping
authors: X
authors: Zhang
authors: Zhili
authors: Z
authors: Yang
authors: Hangxiang
authors: H
authors: Du
authors: Zhenqian
authors: Z
authors: Wu
authors: Jianfeng
authors: J
authors: Gong
authors: Jun
authors: J
authors: Yan
authors: Qi
authors: Q
authors: Zheng
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis*; D054462:p21-Activated Kinases / Q000096:biosynthesis*
chemical_list: D020413:3' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C116367:PAK4 protein, human; D054462:p21-Activated Kinases; D020929:Mitogen-Activated Protein Kinase Kinases