ArticleSignal transduction and targeted therapy2021
UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1β in hepatocellular carcinoma.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Recent Advancements in Known and Emerging Risk Factors of Hepatocellular Carcinoma.Cancer medicine · 2025Pooled it
- Synergistic Anticancer Effects of Lenvatinib and Celastrol via Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress and JNK Signaling in Colon Cancer Cells.Cancer research and treatment · 2026Article
- Article
- NK cell vesicles-based nanoplatform loaded with sorafenib synergizing ferroptosis and antitumor immunity against hepatocellular carcinoma.Journal of nanobiotechnology · 2026Article
- Single-cell and machine learning reveal ROS-associated heterogeneity in hepatocellular carcinoma for precision medicine.BMC cancer · 2026Article
- USP10 confers lenvatinib resistance in hepatocellular carcinoma by deubiquitinating the GPX2.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- AURKA suppresses NCOA4-mediated ferritinophagy to enhance sorafenib resistance in hepatocellular carcinoma.Cell death & disease · 2026Article
- UBQLN1 Inhibition reduces MASH progression through downregulating SIKE/p38 MAPK pathway in hepatocyte.Journal of nanobiotechnology · 2026Article
- Role of mitochondrial dysfunction in muscle wasting in cancer cachexia: a narrative review.Journal of translational medicine · 2026Review
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- Machine Learning-Based Radiopatho-Clinical Model Integrating Ultrasound Radiomics and Kleiner Score for Prognosis Prediction in NAFLD-Related Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Targeting Mitochondrial PD-L1 O-GlcNAcylation to Sensitize HBV-Related HCC to Immunotherapy: Modulating Golgi-mitochondrial Crosstalk and mTOR/PGC-1α-Driven Mitochondrial Biogenesis to Overcome Resistance.International journal of biological sciences · 2026Article
- Integrative discovery and targeted proteomics elucidate the plasma exosomal landscape in thyroid disorders, with emphasis on papillary thyroid carcinoma complicating Hashimoto's thyroiditis.Frontiers in endocrinology · 2026Article
- Exploring the Therapeutic Potential of Plumbagin: Its Current Applications in Cancer and Neuropsychiatric Disorders.Current medicinal chemistry · 2026Review
- Mitochondria Pathway Signature Predicts Prognosis and Therapeutic Response and Identifies REXO2 as a Crucial Regulator in Breast Cancer.Mediators of inflammation · 2026Article
- A Novel MPT-Driven Necrosis-Related lncRNA Signature for Prognostic Prediction in Hepatocellular Carcinoma: Validation Using Organoids.Cancer medicine · 2026Article
- The Role of Mitochondrial Dysfunction in Hepatocellular Carcinoma: From Pathogenesis and Drug Resistance to Targeted Therapeutic Strategies.Journal of hepatocellular carcinoma · 2026Review
- Mitochondria and tumorigenesis: Molecular basis and therapeutic implications.Genes & diseases · 2026Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The treatment for hepatocellular carcinoma (HCC) is promising in recent years, but still facing critical challenges. The first targeted therapy, sorafenib, prolonged the overall survival by months. However, resistance often occurs, largely limits its efficacy. Sorafenib was found to target the electron transport chain complexes, which results in the generation of reactive oxygen species (ROS). To maintain sorafenib resistance and further facilitate tumor progression, cancer cells develop strategies to overcome excessive ROS production and obtain resistance to oxidative stress-induced cell death. In the present study, we investigated the roles of ROS in sorafenib resistance, and found suppressed ROS levels and reductive redox states in sorafenib-resistant HCC cells. Mitochondria in sorafenib-resistant cells maintained greater functional and morphological integrity under the treatment of sorafenib. However, cellular oxygen consumption rate and mitochondria DNA content analyses revealed fewer numbers of mitochondria in sorafenib-resistant cells. Further investigation attributed this finding to decreased mitochondrial biogenesis, likely caused by the accelerated degradation of peroxisome proliferator-activated receptor γ coactivator 1β (PGC1β). Mechanistic dissection showed that upregulated UBQLN1 induced PGC1β degradation in a ubiquitination-independent manner to attenuate mitochondrial biogenesis and ROS production in sorafenib-resistant cells under sorafenib treatment. Furthermore, clinical investigations further indicated that the patients with higher UBQLN1 levels experienced worse recurrence-free survival. In conclusion, we propose a novel mechanism involving mitochondrial biogenesis and ROS homeostasis in sorafenib resistance, which may offer new therapeutic targets and strategies for HCC patients.
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