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.

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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