miR-145 via targeting ERCC2 is involved in arsenite-induced DNA damage in human hepatic cells.

Abstract

Arsenic, an established human carcinogen, causes genetic toxicity. However, the molecular mechanisms involved remain unknown. MicroRNAs (miRNAs) are regulators that participate in fundamental cellular processes. In the present investigation, we selected, as research subjects, patients with arsenic poisoning caused by burning of coal in Guizhou Province, China. For these patients, the plasma levels of miR-145 were up-regulated. In L-02 cells, arsenite, an active form of arsenic, induced up-regulation of miR-145 and down-regulation of ERCC1 and ERCC2, and caused DNA damage. For L-02 cells, transfection with an miR-145 inhibitor prevented arsenite-induced DNA damage and decreased ERCC2 levels. Luciferase reporter assays showed that miR-145 regulated ERCC2 expression by targeting the 3'-UTR of ERCC2, but not that for ERCC1. The present results demonstrate that arsenite induces the over-expression of miR-145 and inhibits DNA repair via targeting ERCC2, thus promoting DNA damage. The information provides a new mechanism for arsenic-induced liver injury.

• Authors: Shaofeng Wei, Junchao Xue, Baofei Sun, Zhonglan Zou, Chao Chen, Qizhan Liu, Aihua Zhang
• Journal: Toxicology letters (Toxicol Lett) Vol. 295 Pg. 220-228 (Oct 01 2018) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 29705342 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• 3' Untranslated Regions
• Arsenites
• DNA-Binding Proteins
• Environmental Pollutants
• MIRN145 microRNA, human
• MicroRNAs
• Sodium Compounds
• sodium arsenite
• ERCC1 protein, human
• Endonucleases
• Xeroderma Pigmentosum Group D Protein
• ERCC2 protein, human

Topics

• 3' Untranslated Regions
• Adult
• Apoptosis (drug effects)
• Arsenic Poisoning (etiology, genetics, metabolism, pathology)
• Arsenites (toxicity)
• Binding Sites
• Case-Control Studies
• Cell Line
• Chemical and Drug Induced Liver Injury (etiology, genetics, metabolism, pathology)
• DNA Damage
• DNA-Binding Proteins (genetics, metabolism)
• Endonucleases (genetics, metabolism)
• Environmental Pollutants (toxicity)
• Female
• Gene Expression Regulation
• Hepatocytes (drug effects, metabolism, pathology)
• Humans
• Liver (drug effects, metabolism, pathology)
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Signal Transduction (drug effects)
• Sodium Compounds (toxicity)
• Xeroderma Pigmentosum Group D Protein (genetics, metabolism)