ArticleInternational journal of biological sciences2024
Negative Regulation of CPSF6 Suppresses the Warburg Effect and Angiogenesis Leading to Tumor Progression Via c-Myc Signaling Network: Potential Therapeutic Target for Liver Cancer Therapy.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Target-site dynamics explain a large share of apparent microRNA differential expression.RNA (New York, N.Y.) · 2026Article
- Oncogene c‑Myc: From molecular mechanism to targeted therapy (Review).Molecular medicine reports · 2026Review
- Targeting aerobic glycolysis combats tyrosine kinase inhibitor resistance of hepatocellular carcinoma.International journal of cancer · 2026Review
- CD8a antibody-functionalized biomimetic red blood cell membrane ectosomes delivering C646 reverse CD8⁺ T Cell exhaustion via H3K18la histone delactylation in gastric cardia adenocarcinoma.Journal of nanobiotechnology · 2026Article
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- CPSF6-mediated alternative polyadenylation of RUNX1 to regulate silica-induced pulmonary fibrosis progression.Respiratory research · 2026Article
- SIRT1 regulates glycolysis and angiogenesis of ovarian cancer through β-catenin/c-Myc/PKM2, and its mechanism in chemotherapy resistance.Frontiers in oncology · 2026Article
- How Traditional Chinese Medicine Works: Biological Mechanisms and Clinical Evidence for Hepatocellular Carcinoma Treatment.Drug design, development and therapy · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- miR-193a-5p-mediated Inhibition of the METTL1/COX-2 axis is critical for Astragalin-induced apoptosis in cervical cancer.Scientific reports · 2025Article
- Daurisoline inhibits glycolysis of lung cancer by targeting the AKT-HK2 axis.Cancer biology & therapy · 2025Article
- Demethoxycurcumin suppresses HK2-mediated glycolysis by targeting PTEN/Akt signaling.Cancer gene therapy · 2025Article
- ZBTB7B modulates the androgen receptor as an upstream regulator via colocalization and direct binding in LNCaP prostate cancer cells.Translational cancer research · 2025Article
- KBTBD11 suppresses hepatocellular carcinoma by targeting ENO1-mediated glycolysis.Journal of translational medicine · 2025Article
- Multifaceted roles of lactate dehydrogenase in liver cancer (Review).International journal of oncology · 2025Review
- Targeting tumor metabolism to augment CD8Journal of pharmaceutical analysis · 2025Review
- Targeting PKM2 in cancer therapeutics: mechanistic advances and translational opportunities.Frontiers in immunology · 2025Review
- Reprogramming of Glucose Metabolism by Nanocarriers to Improve Cancer Immunotherapy: Recent Advances and Applications.International journal of nanomedicine · 2025Review
- Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model.World journal of gastrointestinal oncology · 2024Article
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9 authors.
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Abstract
In this study, we explored the oncogenic mechanism of cleavage and polyadenylation-specific factor 6 (CPSF6) in hepatocellular carcinoma (HCC). CPSF6 was overexpressed in HCC tissues with poor survival rates compared to normal tissues. Hence, CPSF6 depletion suppressed cell viability and colony formation, induced apoptosis via PARP cleavage, and increased the sub-G1 population of Hep3B and Huh7 cells. In addition, CPSF6 enhanced the stability of c-Myc via their binding through nuclear co-localization by binding to c-Myc at the site of 258-360. Furthermore, c-Myc degradation by CPSF6 depletion was disturbed by FBW7 depletion or treatment with the proteasomal inhibitor MG132. Additionally, CPSF6 depletion suppressed the Warburg effect by inhibiting glucose, HK2, PKM2, LDH, and lactate; showed a synergistic effect with Sorafenib in Hep3B cells; and inhibited angiogenesis by tube formation and CAM assays, along with decreased expression and production of vascular endothelial growth factor (VEGF). Notably, CPSF6 depletion attenuated PD-L1 expression and increased Granzyme B levels, along with an increase in the percentage of CD4/CD8 cells in the splenocytes of BALB/c nude mice bearing Hep3B cells. Consistently, immunohistochemistry showed that CPSF6 depletion reduced the growth of Hep3B cells in BALB/c mice in orthotopic and xenograft tumor models by inhibiting tumor microenvironment-associated proteins. Overall, these findings suggest that CPSF6 enhances the Warburg effect for immune escape and angiogenesis, leading to cancer progression via c-Myc, mediated by the HK, PD-L1, and VEGF networks, with synergistic potential with sorafenib as a molecular target for liver cancer therapy.
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