MicroRNA-761 promotes the sensitivity of colorectal cancer cells to 5-Fluorouracil through targeting FOXM1.

Abstract

Resistance to chemotherapy is a big challenge for treatment of patients with colorectal cancer; however; the mechanism underlying chemoresistance in colorectal cancer cell has not been elucidated. MicroRNAs (miRNAs) are new players in the development of drug chemoresistance. In our study, we indicated that overexpression of miR-761 promoted the sensitivity of colorectal cancer cells to 5-Fluorouracil (5-FU). miR-761 expression was downregulated in colorectal cancer cell lines and tissues. miR-761 expression was lower in patients with low grade than in patients with high grade. In additon, we showed that elevated expression of miR-761 suppressed colorectal cancer cell proliferation, cell cycle, colony formation and cell invasion. We identified that FOXM1 was a direct target gene of miR-761 in colorectal cancer cell. FOXM1 expression was upregulated in colorectal cancer tissues compare to the adjacent non-tumor tissues. MiR-761 expression was negatively associated with the expression of FOXM1 in colorectal cancer tissues. Elevated expression of FOXM1 suppressed the sensitivity of miR-761-overexpressing HT29 cells to 5-FU. We also indicated that FOXM1 overexpression promoted cell proliferation, cycle and invasion of miR-761-overexpressing HT29 cells. These data suggested that miR-761 played a tumor suppressor miRNA in colorectal cancer progression and reduced miR-761 expression might be a major mechanism for 5-FU resistance in colorectal cancer cell.