The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

Abstract

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.

Keywords: 5-FU resistance; Colorectal cancer; E-cadherin; PTEN; miR-200c.