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Neuro-oncological ventral antigen 1 regulates liver cancer stem cell properties and Lenvatinib resistance via

Haibing Lan1, Min-Min Sun2, Ping-Sheng Zhou3

  • 1Department of Intensive Care Unit, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China. lhb1520@sina.com.

Cancer Cell International
|December 8, 2025
PubMed

Insights

NOVA1, an RNA binding protein, drives liver cancer stem cell (CSC) self-renewal and tumor growth by stabilizing SOX4 mRNA. Targeting NOVA1 may improve hepatocellular carcinoma (HCC) treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Cancer stem cells (CSCs) are crucial in human cancer development.
  • RNA binding proteins are known to regulate CSC stemness.
  • NOVA1 is identified as an upregulated protein in CSCs.

Purpose of the Study:

  • To investigate the role of NOVA1 in liver CSCs and hepatocellular carcinoma (HCC).
  • To elucidate the mechanism by which NOVA1 affects CSCs.
  • To evaluate NOVA1 as a potential therapeutic target for HCC.

Main Methods:

  • Knockdown and forced expression of NOVA1 in liver CSCs.
  • Mechanistic analysis involving SOX4 mRNA stability and 3'-UTR binding.
  • Assessment of HCC cell response to Lenvatinib treatment.
  • Patient cohort analysis for NOVA1 expression and Lenvatinib efficacy.

Main Results:

  • NOVA1 knockdown inhibited liver CSC tumorigenesis and self-renewal; forced expression had opposite effects.
  • SOX4 was identified as a direct NOVA1 target, with NOVA1 increasing SOX4 mRNA stability.
  • NOVA1 overexpression reduced HCC cell sensitivity to Lenvatinib-induced apoptosis.
  • Low NOVA1 expression potentially predicts Lenvatinib treatment benefits in HCC patients.
  • Knocking down SOX4 reversed NOVA1-mediated Lenvatinib resistance.

Conclusions:

  • NOVA1 plays a critical role in liver CSC self-renewal and tumorigenesis.
  • NOVA1 enhances CSC properties by increasing SOX4 mRNA stability.
  • NOVA1 contributes to Lenvatinib resistance in HCC.
  • NOVA1 represents a promising therapeutic target for HCC.
Keywords:
Hepatocellular carcinoma (HCC)LenvatinibLiver cancer stem cellNOVA1SOX4

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