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

Authors :
Wei S
Xue J
Sun B
Zou Z
Chen C
Liu Q
Zhang A
Source :
Toxicology letters [Toxicol Lett] 2018 Oct 01; Vol. 295, pp. 220-228. Date of Electronic Publication: 2018 Apr 26.
Publication Year :
2018

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.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-3169
Volume :
295
Database :
MEDLINE
Journal :
Toxicology letters
Publication Type :
Academic Journal
Accession number :
29705342
Full Text :
https://doi.org/10.1016/j.toxlet.2018.04.028