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Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
Transcription Factor E2F8 Promotes Cisplatin Resistance in Hepatocellular Carcinoma by Regulating DNA Damage via
Jianqiao Kong1, Song Xu1, Peng Zhang1
1Department of General Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
Abstract:
DNA damage repair has been the key mechanism of cisplatin resistance in hepatocellular carcinoma (HCC). The present study elucidated the molecular mechanism by which nucleolar and spindle-associated protein 1 (NUSAP1) influenced cisplatin tolerance in HCC by regulating DNA damage. First, high mRNA expression of E2F8 and NUSAP1 in HCC was detected by real-time quantitative PCR in cells and tumor tissue. The interaction between E2F8 and NUSAP1 was confirmed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays that E2F8 bound to the promoter region of NUSAP1 and regulated its transcriptional activity. The effects of the E2F8/NUSAP1 axis on cell viability, cell cycle, DNA damage protein γ-H2AX, and cisplatin resistance were investigated by CCK-8, flow cytometry, comet detection, and western blot. The results showed that NUSAP1 knockdown blocked the cell cycle in G0/G1 phase, promoted cisplatin-induced DNA damage, and enhanced cisplatin sensitivity in HCC. Overexpressed E2F8 promoted cell cycle arrest by silencing NUSAP1 in HCC, and promoting DNA damage as well as cisplatin sensitivity. In conclusion, our results suggested that E2F8 enhanced the chemoresistance of HCC cells to cisplatin by activating NUSAP1 to inhibit DNA damage, which provides a basis for describing new therapeutic targets that effectively exacerbate DNA damage and improve the chemical sensitivity of HCC to cisplatin.
Insights
The E2F8/NUSAP1 pathway promotes cisplatin resistance in hepatocellular carcinoma (HCC) by inhibiting DNA damage repair. Targeting this axis could improve chemotherapy effectiveness in HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cisplatin resistance is a major challenge in hepatocellular carcinoma (HCC) treatment.
- DNA damage repair mechanisms are implicated in chemoresistance.
- The role of Nucleolar and Spindle-Associated Protein 1 (NUSAP1) in HCC cisplatin resistance requires elucidation.
Purpose of the Study:
- To investigate the molecular mechanism of NUSAP1 in regulating DNA damage and cisplatin tolerance in HCC.
- To explore the regulatory relationship between E2F8 and NUSAP1 in HCC.
- To assess the therapeutic potential of targeting the E2F8/NUSAP1 axis.
Main Methods:
- Real-time quantitative PCR to detect mRNA expression of E2F8 and NUSAP1.
- Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays to confirm E2F8-NUSAP1 interaction.
- Cell viability (CCK-8), cell cycle (flow cytometry), DNA damage (γ-H2AX, comet assay), and western blot analyses.
Main Results:
- High mRNA expression of E2F8 and NUSAP1 was observed in HCC.
- E2F8 directly binds to and regulates the promoter activity of NUSAP1.
- NUSAP1 knockdown enhanced cisplatin-induced DNA damage and sensitivity in HCC.
- Overexpression of E2F8 promoted cell cycle arrest, increased DNA damage, and enhanced cisplatin sensitivity by silencing NUSAP1.
Conclusions:
- The E2F8/NUSAP1 axis plays a crucial role in regulating DNA damage and cisplatin resistance in HCC.
- E2F8 enhances HCC chemoresistance by activating NUSAP1, which inhibits DNA damage.
- This axis represents a potential therapeutic target to improve cisplatin efficacy in HCC.
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