Transcription factor forkhead box K1 regulates miR-32 expression and enhances cell proliferation in colorectal cancer.

Increased microRNA (miR)-32 expression in colorectal cancer (CRC) tissues enhances CRC cell proliferation, migration, invasion and attenuates CRC cell apoptosis by repressing the expression of phosphatase and tensin homolog (PTEN). Forkhead box K1 (FOXK1) was identified as a potential interacting transcription factor using DNA pull-down assays and mass spectrometry. The present study aimed to elucidate the role of FOXK1 in regulating miR-32 expression in CRC. The expressions of , miR-32, transmembrane protein 245 gene () and were compared between CRC and normal colonic tissues. Levels of miR-32, and the proliferation and apoptosis of CRC cells were studied using FOXK1-overexpression or knockdown, or by simultaneously interfering with FOXK1 and miR-32 expression. Direct FOXK1 binding to the miR-32 promoter was verified using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The results showed elevated , miR-32 and expression, and significantly decreased expression in CRC, compared with normal colonic tissues. Correlations between the expressions of and miR-32, and miR-32, and and were positive and significant. FOXK1-knockdown led to decreased miR-32 and expression and increased PTEN expression, whereas FOXK1-overexpression had the opposite effect. Overexpressed FOXK1 promoted the malignancy of CRC cells by stimulating proliferation and reducing apoptosis; whereas FOXK1-depletion suppressed such malignancy and a miR-32 inhibitor partially reversed the effects of FOXK1. The results of ChIP and dual-luciferase reporter assays indicated that FOXK1 directly binds to the promoter of . Thus, the FOXK1-miR-32-PTEN signaling axis may play a crucial role in the pathogenesis and development of CRC.