Open Access

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

  • Authors:
    • Mayumi Nakamura
    • Masami Hayashi
    • Hiromi Konishi
    • Misa Nunode
    • Keisuke Ashihara
    • Hiroshi Sasaki
    • Yoshito Terai
    • Masahide Ohmichi
  • View Affiliations

  • Published online on: January 23, 2020     https://doi.org/10.3892/ol.2020.11344
  • Pages: 2213-2222
  • Copyright: © Nakamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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March 2020
Volume 19 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Nakamura, M., Hayashi, M., Konishi, H., Nunode, M., Ashihara, K., Sasaki, H. ... Ohmichi, M. (2020). MicroRNA‑22 enhances radiosensitivity in cervical cancer cell lines via direct inhibition of c‑Myc binding protein, and the subsequent reduction in hTERT expression. Oncology Letters, 19, 2213-2222. https://doi.org/10.3892/ol.2020.11344
MLA
Nakamura, M., Hayashi, M., Konishi, H., Nunode, M., Ashihara, K., Sasaki, H., Terai, Y., Ohmichi, M."MicroRNA‑22 enhances radiosensitivity in cervical cancer cell lines via direct inhibition of c‑Myc binding protein, and the subsequent reduction in hTERT expression". Oncology Letters 19.3 (2020): 2213-2222.
Chicago
Nakamura, M., Hayashi, M., Konishi, H., Nunode, M., Ashihara, K., Sasaki, H., Terai, Y., Ohmichi, M."MicroRNA‑22 enhances radiosensitivity in cervical cancer cell lines via direct inhibition of c‑Myc binding protein, and the subsequent reduction in hTERT expression". Oncology Letters 19, no. 3 (2020): 2213-2222. https://doi.org/10.3892/ol.2020.11344