Dose-Response (Mar 2016)

The Role of miR-34a in Tritiated Water Toxicity in Human Umbilical Vein Endothelial Cells

  • Feng Mei Cui,
  • Liang Liu,
  • Lu Lin Zheng,
  • Guang Liang Bao,
  • Yu Tu,
  • Liang Sun,
  • Wei Zhu,
  • Jian Ping Cao,
  • Ping Kun Zhou,
  • Qiu Chen,
  • Yong Ming He

DOI
https://doi.org/10.1177/1559325816638585
Journal volume & issue
Vol. 14

Abstract

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In this work, we investigated the toxic effects of tritiated water (HTO) on the cardiovascular system. We examined the role of microRNA-34a (miR-34a) in DNA damage and repair in human umbilical vein endothelial cells (HUVECs) exposed to HTO. Cell proliferation capacity was evaluated by cell counting, and miR-34a expression was detected using quantitative PCR (QT-PCR). The Comet assay and γ-H2AX immunostaining were used to measure DNA double-strand breaks (DSBs). Reverse transcription polymerase chain reaction was used to measure the expression level of c-myc messenger RNA (mRNA). The cells exposed to HTO showed significantly lower proliferation than the control cells over 3 days. The DNA damage in the HTO group was more severe than that in the control group, at each time point examined. The expression of miR-34a mimics caused increased DNA DSBs whereas that of the miR-34a inhibitor caused decreased DNA DSBs. The proliferation viability was the opposite for the miR-34a mimics and inhibitor groups. The expression levels of c-myc mRNA in cells transfected with miR-34a mimics were lower than that in cells transfected with the miR-34a-5p inhibitor, at 0.5 hours and 2 hours after transfection. In summary, miR-34a mediates HTO toxicity in HUVECs by downregulating the expression of c-myc.