4-Aminobiphenyl (4-ABP) is a recognized human carcinogen. A major source ofexposure to 4-ABP occurs through tobacco smoke and commercial hair dyes.Metabolites of the potent human carcinogen 4-aminobiphenyl (ABP) induce DNAadducts formation that is associated with hepatic and urinary bladder toxicity andbladder tumorigenesis. In our previous study, we demonstrate that miR-513a-5p andmiR-630 play roles in DNA damage response in HepG2 cells following exposure to4-ABP. However, the detailed molecular mechanisms underlying 4-ABP-induced livertoxicity still need to be elucidated. At first, we found that 4-ABP significantly inducedmiR-513a-5p and miR-630 which associated with reactive oxygen species (ROS).Furthermore, transcriptomic analysis (RNA-seq) was observed that the diversebiological functions and metabolic pathways affected included DNA repair activityand cell cycle. We found all the minichromosome maintenance 2–7 (MCM2-7) factorsdecreased in NGS data. The MCM2-7 factors (DNA helicase) play an important rolein DNA replication fork elongation which serves as licensing factors for DNAreplication during S phase. Thereafter, we predicted a number of miR-513a-5p andmiR-630 target genes involved in DNA repair pathways. We combined miRNA targetprediction with NGS data, suggesting that miR-513a-5p and miR-630 mediates MCMmay play a critical role in DNA repair by mediated MCM related proteins expression.These primary results indicated that 4-ABP inhibit DNA repair activity viaROS-dependent, miRNA-assisted MCM related proteins downregulation. Overall, thisstudy examines 4-ABP-induced miRNA generation via ROS and miRNA can inhibitDNA repair activity via MCM related proteins. The goal of this study is to prove(1)4-ABP induce miR-513a-5p and miR-630 production via ROS.(2) miR-513a-5p and miR-630 inhibit MCM 2-7 complex which can inhibit DNArepair activity.(3)In vivo study as in vitro study.
Status | Finished |
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Effective start/end date | 1/08/17 → 31/07/18 |
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In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):