MicroRNA-149 sensitizes colorectal cancer to radiotherapy by downregulating human epididymis protein 4.

Human epididymis protein 4 (HE4) was significantly up-regulated in colorectal cancer (CRC), while the potential relevance to radiation resistance of this phenomenon is still elusive. Relative expressions of target genes were quantified by real-time PCR. The protein level was determined by Western blot. The regulatory effect of miR-149 on WFDC2 (gene encoding HE4 protein) expression was analyzed by luciferase reporter assay. The response to radiation was evaluated by clonogenic assay and xenograft growth . WFDC2 was aberrantly up-regulated and miR-149 was down-regulated in CRC. MiR-149 repressed WFDC2 expression via directly targeting its 3'UTR region. The ectopic expression of miR-149 significantly sensitized CRC to radiation both in vitro and in vivo. Likewise, we further demonstrated that WFDC2-deficiency remarkably improved the radiation resistance in CRC. Simultaneously, WFDC2 rescue completely abolished the radiation sensitivity imposed by miR-149. Our data suggested that miR-149 sensitized CRC to radiation via directly inhibiting WFDC2/HE4, which would hold great promise for future therapeutic exploitations.