4-Aminobiphenyl inhibits the DNA homologous recombination repair in human liver cells: The role of miR-630 in downregulating RAD18 and MCM8
| Autor: | Heng Dao Lin, Chia Yun Lee, Chao-Ling Yao, Ssu Ching Chen, Yi Kuan Tseng, Chung Yi Nien, Fang Zong Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
DNA damage Ubiquitin-Protein Ligases Toxicology CREB Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Aminobiphenyl Compounds Humans DNA Breaks Double-Stranded Epigenetics Cyclic AMP Response Element-Binding Protein Homologous Recombination Transcription factor Minichromosome Maintenance Proteins MCM8 biology Recombinational DNA Repair Free Radical Scavengers Acetylcysteine Cell biology DNA-Binding Proteins MicroRNAs 030104 developmental biology Liver chemistry biology.protein Reactive Oxygen Species Homologous recombination 030217 neurology & neurosurgery DNA |
| Zdroj: | Toxicology. 440:152441 |
| ISSN: | 0300-483X |
| DOI: | 10.1016/j.tox.2020.152441 |
| Popis: | 4-Aminobiphenyl (4-ABP), a well-known human carcinogen, has been shown to cause oxidative DNA damage and induce miR-630 expression in HepG2 cells treated with 18.75 μM-300 μM for 24 h. However, the underlying mechanism regarding the epigenetic regulation of miR-630 on DNA damage repair in liver cells is still not understood and needs to be investigated. In present study, our results showed that miR-630 was upregulated, resulting in mediating a decrease of DNA homologous recombination (HR) repair in L-02, HepG2 or Hep3B cells. Results from a luciferase reporting experiment showed that RAD18 and MCM8 were the potential targets of miR-630 during DNA damage induction. The downregulation of RAD18 or MCM8 by miR-630 was accompanied by inhibition of HR repair. Conversely, inhibiting miR-630 enhanced the expression of RAD18 and MCM8, and rescued HR repair. Additionally, we proved that the transcription factor CREB was related to miR-630 biogenesis in liver cells. Moreover, the levels of CREB, miR-630 expression, and double-strand breaks (DSBs) were attenuated by 5 mM N-acetyl-L-cysteine (NAC) pretreatment, indicating that reactive oxygen species (ROS)-dependent CREB-miR-630 was involved in DSB repair. These findings indicated that the ROS/CREB/-miR-630 axis plays a relevant role in the regulation of RAD18 and MCM8 in HR repair, which may facilitate our understanding of molecular mechanisms regarding the role of miR-630 downregulating DNA damage repair in liver cells. |
| Databáze: | OpenAIRE |
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