MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells

• DOI: 10.1016/j.bbrc.2012.06.123
• Publication Date: 2012-07-02T22:21:24Z
• Authors: Zhigang Wang; Xiaoping Zhang; Zhili Yang; Hangxiang Du; Zhenqian Wu; Jianfeng Gong; Jun Yan; Qi Zheng
• Keywords: Mitogen-Activated Protein Kinase Kinases; 0303 health sciences; Binding Sites; MAP Kinase Signaling System; Apoptosis; 3. Good health; MicroRNAs; 03 medical and health sciences; HEK293 Cells; p21-Activated Kinases; Cell Line, Tumor; Colonic Neoplasms; Humans; 3' Untranslated Regions; Cell Proliferation

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.