ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
PMPCB Silencing Sensitizes HCC Tumor Cells to Sorafenib Therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Platelet-derived microparticles induce CD8Experimental & molecular medicine · 2026Article
- Pmpcb modulates zebrafish neurogenesis and stress resistance via regulating mitochondria metabolism and function.Molecular neurobiology · 2026Article
- Mitochondrial alterations and signatures in hepatocellular carcinoma.Cancer metastasis reviews · 2025Review
- Proteomic Analysis Highlights the Impact of the Sphingolipid Metabolizing Enzyme β-Galactosylceramidase on Mitochondrial Plasticity in Human Melanoma.International journal of molecular sciences · 2024Article
- Progress and application of lung-on-a-chip for lung cancer.Frontiers in bioengineering and biotechnology · 2024Review
- Investigation of the Proteasome 26S Subunit, ATPase Family Genes as Potential Prognostic Biomarkers and Therapeutic Targets for Hepatocellular Carcinoma.Cancer management and research · 2024Article
- Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy.Drug delivery · 2022Article
- Article
- Mitochondrial Processing Peptidases-Structure, Function and the Role in Human Diseases.International journal of molecular sciences · 2022Review
- Degradome-focused RNA interference screens to identify proteases important for breast cancer cell growth.Frontiers in oncology · 2022Article
- Nano Drug Delivery System for Tumor Immunotherapy: Next-Generation Therapeutics.Frontiers in oncology · 2022Review
- TRERNA1 upregulation mediated by HBx promotes sorafenib resistance and cell proliferation in HCC via targeting NRAS by sponging miR-22-3p.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated β-catenin/ABCB1 signaling pathway.Journal of biomedical science · 2021Article
- Recent Progress in Understanding the Action of Natural Compounds at Novel Therapeutic Drug Targets for the Treatment of Liver Cancer.Frontiers in oncology · 2021Review
- Elucidating the Molecular Basis of Sorafenib Resistance in HCC: Current Findings and Future Directions.Journal of hepatocellular carcinoma · 2021Review
- Mitochondrial Quality Control in Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Exploring the mechanism of resistance to sorafenib in two hepatocellular carcinoma cell lines.Aging · 2020Article
- New Therapeutic Options for Advanced Hepatocellular Carcinoma.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) tumors invariably develop resistance to cytotoxic and targeted agents, resulting in failed treatment and tumor recurrence. Previous in vivo short hairpin RNA (shRNA) screening evidence revealed mitochondrial-processing peptidase (PMPC) as a leading gene contributing to tumor cell resistance against sorafenib, a multikinase inhibitor used to treat advanced HCC. Here, we investigated the contributory role of the β subunit of PMPC (PMPCB) in sorafenib resistance. Silencing PMPCB increased HCC tumor cell susceptibility to sorafenib therapy, decreased liver tumor burden, and improved survival of tumor-bearing mice receiving sorafenib. Moreover, sorafenib + PMPCB shRNA combination therapy led to attenuated liver tumor burden and improved survival outcome for tumor-bearing mice, and it reduced colony formation in murine and human HCC cell lines in vitro. Additionally, PMPCB silencing enhanced PINK1-Parkin signaling and downregulated the anti-apoptotic protein MCL-1 in sorafenib-treated HCC cells, which is indicative of a healthier pro-apoptotic phenotype. Higher pre-treatment MCL-1 expression was associated with inferior survival outcomes in sorafenib-treated HCC patients. Elevated MCL-1 expression was present in sorafenib-resistant murine HCC cells, while MCL-1 knockdown sensitized these cells to sorafenib. In conclusion, our findings advocate combination regimens employing sorafenib with PMPCB knockdown or MCL-1 knockdown to circumvent sorafenib resistance in HCC patients.
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