MicroRNA-145 induces cell cycle arrest in G1 phase by directly targeting KLF5 in colon cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-associated mortality worldwide. There is increasing evidence that microRNAs (miRNAs) are involved in development and progression of colorectal carcinoma. miR-145 is a tumor suppressor and has been confirmed as a negative regulator of colorectal cancer. Although multiple target genes have been identified for miR-145, the molecular mechanism by which it inhibits colon cancer is still unknown. Here, we used bioinformatic analysis and a reporter assay to identify KLF5, a putative oncoprotein in colon cancer, as a potential direct target of miR-145. Ectopic expression of mir-145 robustly decreased the expression of KLF5 proteins in in CRC tissues and cell lines. Furthermore, overexpression of miR-145 induced cell cycle arrest in the G1 phase colon cancer cells. This phenomenon was consistent with siRNA-mediated down-regulation of KLF5 in colon cancer cells. Additionally, we performed a rescue experiment to demonstrate that the reexpression of KLF5 partially attenuated cell cycle arrest in the G1 phase in miR-145 transfected colon cancer cells. Real-time PCR analysis of colon cancer cell lines showed an inverse relationship between expressions of miR-145 and KLF5, providing a plausible explanation that high level KLF5 activation in colon carcinoma may be due to the reduction of miR-145. Our study demonstrated for the first time that miR-145 induces cell cycle arrest in the G1 phase by directly targeting KLF5 in colon cancer cells; further emphasizing that miR-145 may be a promising candidate in colorectal cancer therapeutics.