2. Academic Validation
  3. circRNA-SORE/UBQLN1/GPX4 Mediates the Acquisition of Sorafenib Resistance in Hepatocellular Carcinoma Through Inhibition of Ferroptosis

circRNA-SORE/UBQLN1/GPX4 Mediates the Acquisition of Sorafenib Resistance in Hepatocellular Carcinoma Through Inhibition of Ferroptosis

  • MedComm (2020). 2025 Nov 23;6(12):e70488. doi: 10.1002/mco2.70488.
Lin Ji 1 2,  Yeling Ruan 2 3,  Meng Tong 1 2,  Tianyi Chen 2 4,  Jingwei Cai 2 5,  Zhengtao Ye 1 2,  Xiujun Cai 1 2,  Junjie Xu 1 2
Affiliations

Affiliations

  • 1 Department of General Surgery Sir Run-Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China.
  • 2 National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China.
  • 3 Department of Head and Neck Surgery Sir Run-Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China.
  • 4 Plastic & Aesthetic Center Sir Run-Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China.
  • 5 Department of Thoracic Surgery Sir Run-Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China.
PMID: 41287824 DOI: 10.1002/mco2.70488
Abstract

The clinical performance of targeted therapies for treating hepatocellular carcinoma (HCC) is significantly limited by the frequent emergence of drug resistance, ultimately resulting in therapeutic failure and poor prognosis. While the precise mechanisms underlying this resistance are not fully elucidated. Emerging evidence implicated that Reactive Oxygen Species (ROS) homeostasis and Ferroptosis, a unique form of programmed cell death, are closely associated with the development of drug resistance in Cancer cells. In this study, we demonstrated that circRNA-SORE, a circRNA previously reported by our group, played a crucial role in mediating sorafenib resistance via regulating intracellular ROS levels and inhibiting Ferroptosis. Mechanically, we identified that circRNA-SORE exerted its regulatory effects through modulating the level of UBQLN1. UBQLN1, via its STI domain, stabilized GPX4, a crucial antioxidant enzyme that protects against Ferroptosis death. The stabilization of GPX4 promoted Cancer cell survival under sorafenib-induced oxidative stress. In conclusion, this study revealed a novel circRNA-SORE/UBQLN1/GPX4 regulatory axis that mediated sorafenib resistance in HCC and also offered a promising therapeutic strategy to overcome drug resistance and improve clinical outcomes for patients with HCC.

Keywords

UBQLN1:GPX4; circRNA; ferroptosis; sorafenib resistance.

Figures
Products
Inhibitors & Agonists
Other Products