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 journalArticle

6 Citations (Scopus)

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 - 2014

Fingerprint

Ionizing Radiation
MicroRNAs
ionizing radiation
inhibitors
inhibitor
cancer
Epithelial Cells
cultured cells
Colonic Neoplasms
mice
irradiation
Solar Activity
Radiation
Cell Line
Small Untranslated RNA
Radiation Tolerance
radiation tolerance
radiation
targeting
RNA

Keywords

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

ASJC Scopus subject areas

  • Astronomy and Astrophysics
  • Radiation
  • Health, Toxicology and Mutagenesis
  • Ecology

Cite this

Inhibition of microRNA-31-5p protects human colonic epithelial cells against ionizing radiation. / Kim, Sang Bum; Zhang, Lu; Barron, Summer; Shay, Jerry W.

In: Life Sciences in Space Research, Vol. 1, No. 1, 2014, p. 67-73.

Research output: Contribution to journalArticle

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