Epigenetic Regulation of Micror-513a-5p and Mir-630 Expression of Dna Repair Pathways in 4-Abp Treated Human Hepatoma Cells and C57bl/6 Mice

Project Details

Description

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.
StatusFinished
Effective start/end date1/08/1731/07/18

UN Sustainable Development Goals

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):

  • SDG 3 - Good Health and Well-being
  • SDG 11 - Sustainable Cities and Communities
  • SDG 17 - Partnerships for the Goals

Keywords

  • 4-ABP
  • ROS
  • miR-513a-5p
  • miR-630
  • MCM 2-7 complex
  • DNA repair

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