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Updated: May 13, 2025

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CircRNA-mTOR Promotes Hepatocellular Carcinoma Progression and Lenvatinib Resistance Through the PSIP1/c-Myc Axis

Yongchang Tang1,2, Feng Yuan1,3, Mingbo Cao1

  • 1Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 15, 2025
PubMed

Insights

Circular RNAs (circRNAs) regulate drug resistance in hepatocellular carcinoma (HCC). This study identifies circRNA-mTOR as a key driver of HCC progression and lenvatinib resistance via the PSIP1/c-Myc pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (circRNAs) are implicated in drug resistance in hepatocellular carcinoma (HCC).
  • The precise mechanisms driving resistance and hindering HCC treatment efficacy require further elucidation.
  • Understanding these mechanisms is critical for developing more effective therapeutic strategies.

Purpose of the Study:

  • To investigate the role of circRNA-mTOR in hepatocellular carcinoma (HCC) progression and lenvatinib resistance.
  • To elucidate the molecular mechanisms by which circRNA-mTOR influences HCC stemness and drug resistance.
  • To evaluate circRNA-mTOR as a potential biomarker for HCC diagnosis and prognosis.

Main Methods:

  • Quantitative analysis of circRNA-mTOR expression in HCC tissues.
  • Investigation of circRNA-mTOR's effects on HCC cell stemness and lenvatinib sensitivity.
  • Mechanistic studies involving RNA-binding protein (RBP) nuclear translocation and signaling pathway analysis (PSIP1/c-Myc).

Main Results:

  • CircRNA-mTOR is highly expressed in HCC and correlates with poor patient prognosis.
  • CircRNA-mTOR enhances HCC cell stemness, promotes HCC progression, and confers lenvatinib resistance.
  • Mechanistically, circRNA-mTOR facilitates PSIP1 nuclear translocation, activating the PSIP1/c-Myc pathway.

Conclusions:

  • CircRNA-mTOR plays a significant role in HCC progression and lenvatinib resistance.
  • CircRNA-mTOR serves as a potential diagnostic and prognostic biomarker for HCC.
  • Targeting circRNA-mTOR may offer a novel therapeutic strategy to overcome lenvatinib resistance in HCC.
Keywords:
Lenvatinib resistancePSIP1circRNAc‐Mychepatocellular carcinoma

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