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Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells

Lv Chen1, Shu Yang2, Cong Wen3

  • 1Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. chenlv@csu.edu.cn.

Toxins
|March 17, 2019
PubMed

Insights

Microcystin-LR (MC-LR) causes liver damage. Increased miR-451a protects against MC-LR-induced DNA damage by down-regulating p-AKT1, offering new insights for liver injury diagnosis and therapy.

Area of Science:

  • Hepatotoxicity
  • Molecular Biology
  • Toxicology

Background:

  • Microcystin-LR (MC-LR) is a cyanobacterial hepatotoxin.
  • Previous studies indicated altered microRNA expression, including miR-451a, in liver cells exposed to MC-LR.
  • The role of miR-451a in MC-LR-induced liver injury was previously unclear.

Purpose of the Study:

  • To investigate the functional role of miR-451a in normal human liver cells (HL7702) exposed to MC-LR.
  • To determine the impact of miR-451a modulation on MC-LR-induced cellular damage.
  • To elucidate the molecular mechanisms underlying miR-451a's protective effects against MC-LR.

Main Methods:

  • HL7702 cells were treated with varying concentrations of MC-LR (5 and 10 μM).
  • Comet assay was employed to assess DNA damage (Olive tail moment).
  • Quantitative analysis of miR-451a, γ-H2AX, and p-AKT1 protein expression levels was performed.

Main Results:

  • MC-LR exposure was shown to induce DNA damage in HL7702 cells, as indicated by increased Olive tail moment.
  • Upregulation of miR-451a significantly repressed MC-LR-induced DNA damage and γ-H2AX protein expression.
  • Overexpression of miR-451a inhibited the expression of p-AKT1 protein in MC-LR-treated cells.

Conclusions:

  • miR-451a plays a protective role against MC-LR-induced DNA damage in liver cells.
  • This protection is mediated, at least in part, by the down-regulation of p-AKT1 expression.
  • These findings provide novel insights for the diagnosis and therapeutic strategies for MC-LR-induced liver injury.
Keywords:
AKT1DNA damagemiR-451amicrocystin-LR

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