MicroRNA regulation of DNA repair gene expression in 4-aminobiphenyl-treated HepG2 cells

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Title:	MicroRNA regulation of DNA repair gene expression in 4-aminobiphenyl-treated HepG2 cells
Authors:	陳師慶;Huan, Lin Chen;Wu, Jong-C.;Chiou, Bin-Hao;Chen, Chin-Hui;Ma, Nianhan;Chang, Chi Yao;Tsen, Yi-Kuang;Chen, Ssu Ching
Contributors:	生醫理工學院生命科學系
Keywords:	Aminobiphenyl Compounds - toxicity;Arrays;bioinformatics;Blotting, Western;carcinogens;Carcinogens - toxicity;Cell Survival - drug effects;Comet Assay;Culture Media;Damage;Deoxyribonucleic acid;DNA;DNA Damage;DNA repair;DNA Repair - genetics;Emergency;Gene expression;Gene Expression - drug effects;gene expression regulation;gene overexpression;Genes;human cell lines;Humans;In Situ Hybridization;microRNA;miRNA-513a-5p;miRNA-630;proliferating cell nuclear antigen;Proteins;quantitative polymerase chain reaction;Real-Time Polymerase Chain Reaction;Repair;reverse transcriptase polymerase chain reaction;Ribonucleic acids;RNA - biosynthesis;RNA - isolation & purification;RNA, Messenger - biosynthesis;RNA, Messenger - physiology
Date:	2014-08-01
Issue Date:	2026-04-23 11:13:22 (UTC+8)
Publisher:	Elsevier Ireland Ltd;Ireland: Elsevier Ireland Ltd
Abstract:	摘要： We examined the role of miRNAs in DNA damage response in HepG2 cells following exposure to 4-aminobiphenyl (4-ABP). The arylamine 4-ABP is a human carcinogen. Using the Comet assay, we showed that 4-ABP (18.75–300μM) induces DNA damage in HepG2 cells after 24h. DNA damage signaling pathway-based PCR arrays were used to investigate expression changes in genes involved in DNA damage response. Results showed down-regulation of 16 DNA repair-related genes in 4-ABP-treated cells. Among them, the expression of selected six genes (UNG, LIG1, EXO1, XRCC2, PCNA, and FANCG) from different DNA repair pathways was decreased with quantitative real-time PCR (qRT-PCR). In parallel, using the miRNA array, we reported that the expression of 27 miRNAs in 4-ABP-treated cells was at least 3-fold higher than that in the control group. Of these differential 27 miRNAs, the most significant expression of miRNA-513a-5p and miRNA-630 was further validated by qRT-PCR, and was predicted to be implicated in the deregulation of FANCG and RAD18 genes, respectively, via bioinformatic analysis. Both FANCG and RAD18 proteins were found to be down-regulated in 4-ABP-treated cells. In addition, overexpression and knockdown of miRNA-513a-5p and miRNA-630 reduced and increased the expression of FANCG and RAD18 proteins, respectively. Based on the above results, we indicated that miRNA-513a-5p and miRNA-630 could play a role in the suppression of DNA repair genes, and eventually lead to DNA damage. 其他題名： Toxicology 出版者： Ireland: Elsevier Ireland Ltd 出版日期： 2014-08-01 出處： Toxicology (Amsterdam), 2014-08, Vol.322, p.69-77 版權： 2014 Elsevier Ireland Ltd 版權： Elsevier Ireland Ltd 版權： Copyright © 2014 Elsevier Ireland Ltd. All rights reserved. 識別號： ISSN: 0300-483X 識別號： ISSN: 1879-3185 識別號： EISSN: 1879-3185 識別號： DOI: 10.1016/j.tox.2014.05.003 識別號： PMID: 24857880
Appears in Collections:	[Department of Life Science] journal & Dissertation

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