miR-361 enhances sensitivity to 5-fluorouracil by targeting the FOXM1-ABCC5/10 signaling pathway in colorectal cancer.

Colorectal cancer (CRC) is one of most common malignancies worldwide. 5-fluorouracil (5-FU) is a mainstay of CRC treatment, particularly in patients with advanced stages of the disease; however, 5-FU-based chemotherapy is not always effective and may result in progression of the disease. The present study investigated several candidate microRNAs (miRs) in parental and 5-FU-resistant HCT116 and HT29 cells, and identified miR-361 as a novel regulator of chemosensitivity. Overexpression of miR-361 enhanced the 5-FU susceptibility of parental and resistant HCT116 and HT29 cells . Impaired colony formation capacity and increased cell apoptosis (as determined via flow cytometry) was observed in resistant HCT116 and HT29 cells. Furthermore, forkhead box M1 (FOXM1) was identified as a target gene of miR-361 using a dual-luciferase reporter assay, western blotting and reverse transcription-quantitative PCR. Additionally, FOXM1 knockdown improved the cytotoxicity of 5-FU in resistant CRC. ATP binding cassette subfamily C members 5 and 10 (ABCC5/10) were found to be downstream effectors of miR-361. In conclusion, miR-361 increased chemosensitivity, at least in part, via modulation of FOXM1-ABCC5/10. miR-361 may serve as a potential therapeutic target for patients with CRC.