Inhibition of microRNA-31-5p protects human colonic epithelial cells against ionizing radiation

Sang Bum Kim, Lu Zhang, Summer Barron, Jerry W. Shay

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

MicroRNAs (miRNAs), endogenous non-coding small RNAs, are sensitive to environmental changes, and their differential expression is important for adaptation to the environment. However, application of miRNAs as a clinical prognostic or diagnostic tool remains unproven. In this study we demonstrate a chronic/persistent change of miRNAs from the plasma of a colorectal cancer susceptible mouse model (CPC;Apc) about 250 days after exposure to a simulated solar particle event (SPE). Differentially expressed miRNAs were identified compared to unirradiated control mice, including miR-31-5p, which we investigated further. To address the cellular function of miR-31-5p, we transfected a miR-31-5p mimic (sense) or inhibitor (antisense) into immortalized human colonic epithelial cells followed by gamma-irradiation. A miR-31-5p mimic sensitized but a miR-31-5p inhibitor protected colonic epithelial cells against radiation induced killing. We found that the miR-31-5p mimic inhibited the induction of hMLH1 expression after irradiation, whereas the miR-31-5p inhibitor increased the basal level of hMLH1 expression. The miR-31-5p inhibitor failed to modulate radiosensitivity in an hMLH1-deficient HCT116 colon cancer cell line but protected HCT116 3-6 and DLD-1 (both hMLH1-positive) colon cancer cell lines. Our findings demonstrate that miR-31-5p has an important role in radiation responses through regulation of hMLH1 expression. Targeting this pathway could be a promising therapeutic strategy for future personalized anti-cancer radiotherapy.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalLife Sciences in Space Research
Volume1
Issue number1
DOIs
StatePublished - Apr 2014

Keywords

  • Human colonic epithelial cells (HCECs)
  • Human mutL homologue-1 (hMLH1)
  • MiR-31-5p
  • Radioprotection
  • Solar Particle Event (SPE)

ASJC Scopus subject areas

  • Radiation
  • Ecology
  • Astronomy and Astrophysics
  • Agricultural and Biological Sciences (miscellaneous)
  • Health, Toxicology and Mutagenesis

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