Over-expression of miR-15a-3p enhances the radiosensitivity of cervical cancer by targeting tumor protein D52

Biomed Pharmacother. 2018 Sep;105:1325-1334. doi: 10.1016/j.biopha.2018.06.033. Epub 2018 Jun 26.

Abstract

Background: Radioresistance is a challenge in the treatment of cervical cancer. Recent studies have reported that microRNAs (miRNAs) mediate radiotherapy resistance and play a vital role in the occurrence and development of cancer. The aim of this study was to investigate whether the expression of miR-15a-3p was correlated with radiosensitivity in cervical cancer.

Methods: Quantitative real-time PCR experiment was performed to detect the expression of miR-15a-3p in cervical cancer tissues and cells lines. Then, the effect of miR-15a-3p on proliferation in cervical cancer cells radiation-induced were determined by using CCK-8, clonogenic formation and EdU assays. In addition, the TUNEL, flow cytometry analysis and western blotting assays were conducted to evaluate radiation-induced cells apoptosis. A dual-luciferase reporter assay was used to test the target. In addition, tumor xenograft experiment was conducted to test tumor growth in vivo.

Results: In this study, miR-15a-3p was downregulated in cervical cancer tissues and cells lines, however, the expression of miR-15a-3p significantly increased exposed to radiation. Moreover, over-expression of miR-15a-3p inhibited cells proliferation and enhanced cells apoptosis radiation-induced. Further, TPD52 was identified as a direct target of miR-15a-3p. Inhibition of TPD52 could suppress cells proliferation and induce cells apoptosis. Tumor xenograft experiments indicated that over-expression of miR-15a-3p could increase sensitivity to radiation therapy by targeting TPD52.

Conclusion: In conclusion, our findings suggested that miR-15a-3p enhanced radiosensitivity in cervical cancer by targeting tumor protein D52, suggesting that miR-15a-3p may be a potential therapeutic target for cervical cancer patients.

Keywords: Cervical cancer; Radiosensitivity; Tumor protein D52; miR-15a-3p.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • In Situ Nick-End Labeling / methods
  • MicroRNAs / genetics*
  • Neoplasm Proteins / genetics*
  • Radiation Tolerance / genetics*
  • Uterine Cervical Neoplasms / genetics*

Substances

  • MIRN15 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • TPD52 protein, human