Circular RNA circUBE2D2 functions as an oncogenic factor in hepatocellular carcinoma sorafenib resistance and

Hai Huang1, Jian Peng2, Shijian Yi3

  • 1Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital Nanning 530199, China.

Insights

Circular RNAs (circRNAs) promote hepatocellular carcinoma (HCC) glycolysis and sorafenib resistance by regulating the miR-889-3p/LDHA axis. Targeting circUBE2D2 offers a potential new strategy for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (circRNAs) influence hepatocellular carcinoma (HCC) progression and chemoresistance.
  • The specific molecular mechanisms of circRNA-mediated sorafenib resistance in HCC are not fully understood.

Purpose of the Study:

  • To investigate the role of circUBE2D2 in HCC sorafenib resistance and tumor progression.
  • To elucidate the underlying molecular mechanism involving the miR-889-3p/LDHA axis.

Main Methods:

  • Correlation analysis between circUBE2D2 expression and HCC patient survival.
  • In vitro functional assays to assess the impact of circUBE2D2 on glycolysis and sorafenib resistance.
  • In vivo tumor growth experiments following circUBE2D2 knockdown.
  • Mechanism studies involving circRNA localization, microRNA sponging, and mRNA targeting.

Main Results:

  • Elevated circUBE2D2 expression correlates with reduced survival rates in HCC patients.
  • circUBE2D2 promotes glycolysis (Warburg effect) and sorafenib resistance in vitro.
  • Knockdown of circUBE2D2 inhibits tumor growth in vivo.
  • circUBE2D2 acts as a molecular sponge for miR-889-3p, leading to increased LDHA expression.

Conclusions:

  • circUBE2D2 accelerates HCC glycolysis and sorafenib resistance through the circUBE2D2/miR-889-3p/LDHA pathway.
  • This pathway represents a novel therapeutic target for overcoming sorafenib resistance in HCC.

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