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miR-145 via targeting ERCC2 is involved in arsenite-induced DNA damage in human hepatic cells.
- 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.)
- Subjects :
- 3' Untranslated Regions
Adult
Apoptosis drug effects
Arsenic Poisoning genetics
Arsenic Poisoning metabolism
Arsenic Poisoning pathology
Binding Sites
Case-Control Studies
Cell Line
Chemical and Drug Induced Liver Injury genetics
Chemical and Drug Induced Liver Injury metabolism
Chemical and Drug Induced Liver Injury pathology
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Endonucleases genetics
Endonucleases metabolism
Female
Gene Expression Regulation
Hepatocytes metabolism
Hepatocytes pathology
Humans
Liver metabolism
Liver pathology
Male
MicroRNAs genetics
Middle Aged
Signal Transduction drug effects
Xeroderma Pigmentosum Group D Protein genetics
Arsenic Poisoning etiology
Arsenites toxicity
Chemical and Drug Induced Liver Injury etiology
DNA Damage
Environmental Pollutants toxicity
Hepatocytes drug effects
Liver drug effects
MicroRNAs metabolism
Sodium Compounds toxicity
Xeroderma Pigmentosum Group D Protein metabolism
Subjects
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