Open AccessMicroRNA‑22 enhances radiosensitivity in cervical cancer cell lines via direct inhibition of c‑Myc binding protein, and the subsequent reduction in hTERT expression
Author(s) -
Mayumi Nakamura,
Masami Hayashi,
Hiromi Konishi,
Misa Nunode,
Kaoru Ashihara,
Hiroshi Sasaki,
Yoshito Terai,
Masahide Ohmichi
Publication year - 2020
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2020.11344
Subject(s) - telomerase reverse transcriptase , clonogenic assay , cancer research , oncogene , radiosensitivity , downregulation and upregulation , microrna , biology , gene silencing , telomerase , cell cycle , cancer , microbiology and biotechnology , cell culture , gene , medicine , radiation therapy , genetics
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.