Down-regulation of miR-543 expression increases the sensitivity of colorectal cancer cells to 5-Fluorouracil through the PTEN/PI3K/AKT pathway

Resistance to chemotherapy is one of main obstacles in the treatment of colorectal cancer (CRC). However, the mechanisms are still unclear, and the treatment options are still limited. miR-543 has been indicated to act as an oncogene in some cancers, but its function in regulating chemoresistance has not been considered in CRC cells. This study investigated whether the down-regulation of miR-543 expression enhanced 5-fluorouracil (5-FU)-induced apoptosis in HCT8/FU colon cancer cells. In our study, qRT-PCR revealed that miR-543 expression was up-regulated in the HCT8/FU colon cancer cell line compared with that of HCT8 colon cancer cell line. An miR-543 inhibitor or mimic was transfected, followed by MTT assay to detect 5-FU sensitivity in HCT8 and HCT8/FU cell lines, which showed that IC(50) of 5-FU was positively correlated with miR-543 expression. Further studies showed that miR-543 enhanced drug resistance by down-regulating the expression of phosphatase and tensin homolog (PTEN), which negatively regulates protein kinase B (AKT) activation. Additionally, an elevated expression of PTEN reversed the chemoresistance of miR-543-overexpressing HCT8 cells to 5-FU. These results indicate that miR-543 might be a target to increase the sensitivity of CRC cells to 5-FU through the PTEN/PI3K/AKT pathway.