MicroRNA-22 enhances radiosensitivity in cervical cancer cell lines via direct inhibition of c-Myc binding protein, and the subsequent reduction in hTERT expression.

Abstract

MicroRNAs (miRs) influence the expression of their target genes post-transcriptionally and serve an important role in multiple cellular processes. The downregulation of miR-22 is associated with a poor prognosis in cervical cancer. However, the mechanisms underlying miR-22-mediated gene regulation and its function are yet to be elucidated. In the present study, the effect of miR-22 expression on the radiosensitivity of cervical cancer was investigated. First, miR-22 was either up- or downregulated to evaluate the regulation of the MYC-binding protein (MYCBP) in four cervical cancer cell lines (C-4I, SKG-II and SiHa). Notably, MYCBP expression was inversely associated with miR-22 induction. A dual-luciferase reporter gene assay revealed that miR-22 directly targets the MYCBP 3′-untranslated region. Subsequently, the level of human telomerase reverse transcriptase component (hTERT; an E-box-containing c-Myc target gene) was analyzed after the up- or downregulation of miR-22. Notably, miR-22-mediated repression of MYCBP reduced hTERT expression. In addition, the influence of miR-22 on radiosensitivity in C-4I, SKG-II and SiHa cells was examined using a clonogenic assay and in mouse xenograft models. Upregulation of miR-22 was associated with increased radiosensitivity. Furthermore, lentiviral transduction of miR-22 reduced the Ki-67 index while increasing the TUNEL index in xenograft tissue. The current findings indicate the potential utility of miR-22 in radiotherapy for cervical cancer.