| 摘要: | 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 |
