miR-375-3p suppresses cell proliferation and 5FU resistance of CRC cells by repressing YAP1 and SP1. (A) Overexpression of YAP1 and SP1increased cells resistance to 5FU in CRC parental cell lines, HCT116 and HCT8. (B) Depletion of YAP1 and SP1 reversed cells resistance to5FU in CRC resistant cell lines, HCT116/FU and HCT8/FU. (C, D) Cell viability assays were measured both in parental cell lines (HCT116, HCT8) and 5FU-resistant cell lines (HCT116/FU, HCT8/FU). HCT116 and HCT8 cells co-transfected with miR-375-3p inhibitors and siYAP1 or siSP1 respectively, were treated with 5FU (10μg/ml) or not (PBS). HCT116/FU and HCT8/FU cells co-transfected with miR-375-3p and YAP1 or SP1 overexpressing plasmids respectively, were treated with 5FU (50μg/ml) or not (PBS). (E, F) The apoptosis rates of HCT116/FU cells with co-transfection of miR-375-3p inhibitors and siYAP1 or siSP1, respectively, and HCT8/FU cells with co-transfection of miR-375-3p and YAP1 or SP1 overexpressing plasmids, respectively, were measured by flow cytometry analysis. Every system treated with low dose of 5FU for 50μg/ml. *P < 0.05, **P < 0.01 and ***P < 0.001.