miR-34a increases the sensitivity of colorectal cancer cells to 5-fluorouracil in vitro and in vivo.

This study was designed to investigate the significance of the effect of miR-34a on 5-fluorouracil (5-FU) sensitivity in vitro and in vivo. miR-34a expression in tumor tissues or serum was determined by quantitative polymerase chain reaction. CRC cell lines HCT116 and SW480 were used to evaluate cell viability, cell apoptosis, and the cell cycle using a cell proliferation assay, flow cytometry, and Western blotting, respectively. For the in vivo studies, xenografts derived from SW480 cells were established to assess the antitumor activity between miR-34a and 5-FU. Patients with high levels of miR-34a expression were found to benefit more from 5-FU-based chemotherapy than patients with low levels of miR-34a expression, regardless of disease stage. Ectopic expression of miR-34a alone or 5-FU alone was found to inhibit CRC cell growth in vitro and in vivo. Moreover, cell growth in vitro and in vivo was further inhibited when miR-34a combined with 5-FU through increasing the rate of cell apoptosis. The potential targets of miR-34a, including CREB1, Bcl-2, Notch 1, Sirt1, and E2F3, were predicted and preliminarily validated and merit further study.
CONCLUSION: miR-34a might function as a predictor of fluorouracil chemosensitivity in CRC, and a combination strategy of miR-34a with fluorouracil was expected to be more beneficial for CRC patients.