ArticleMolecular cancer2023
A novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triple-negative breast cancer.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Pooled it
- Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches.International journal of molecular sciences · 2024Pooled it
- Application and prospect of organoid technology in breast cancer.Frontiers in immunology · 2024Pooled it
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- Microproteins as a Hidden Player in Breast Cancer: From Molecular Insights to Therapeutic Potential.Cell biochemistry and function · 2026Review
- The translational roles of circular RNAs in cancers and their underlying molecular mechanisms.Medical oncology (Northwood, London, England) · 2026Review
- circOMA1 delivered by exosomes regulates DRD2‑mediated prolactinoma resistance.International journal of molecular medicine · 2026Article
- Decoding the functional network of circular RNAs encoding proteins in hepatocellular carcinoma: from carcinogenesis to clinical transformation.Journal of advanced research · 2026Review
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- NAA50-mediated SLU7 stabilization promotes cisplatin resistance in bladder cancer via regulating MAP3K3 mRNA nuclear export and p38 MAPK activation.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- PCMTD1-127aa suppresses osteosarcoma progression by competitively binding to USP10 to promoteiScience · 2026Article
- A novel peptide MIB1-223aa encoded by exosomal circMIB1 from cancer-associated fibroblasts drives triple-negative breast cancer metastasis and stemness via stabilizing MIB1 to activate Notch signaling.Journal of advanced research · 2026Article
- Review
- CAPG serves as a prognostic biomarker and promotes proliferation and migration in pancreatic ductal adenocarcinoma.PloS one · 2026Article
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- CircLRBA Promotes Epithelial-Mesenchymal Transition, Immune Evasion, Chemoimmunotherapy Resistance and Metastasis Through Stabilizing Twist1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Circular RNA CLASP1 modulates the GLI1/SNAIL axis and enhances macrophage polarization in breast cancer.Oncogene · 2025Article
- CircSMEK1 Suppresses HCC via the hnRNPK-IGF2-AKT Axis: A Diagnostic Biomarker and Therapeutic Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Establishment and characterization of an orthotopic implanted lung cancer model to mimic human tumor structure, microenvironment, and metastatic spread.Translational lung cancer research · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe treatment of Triple-negative breast cancer (TNBC) has always been challenging due to its heterogeneity and the absence of well-defined molecular targets. The present study aims to elucidate the role of protein-coding circRNAs in the etiology and carcinogenesis of TNBC.
methodsCircRNA expression data in TNBC (GEO: GSE113230, GSE101123) were reanalyzed and then circCAPG was selected for further study. To identify the polypeptide-coding function of circCAPG, a series of experiments, such as Mass spectrometry and dual-luciferase reporter assays were conducted. Cell proliferation, apoptosis and metastasis parameters were determined to investigate the cancerous functions CAPG-171aa plays in both TNBC organoids and nude mice. Mechanistically, the relation between CAPG-171aa and STK38 in TNBC was verified by immunoprecipitation analyses and mass spectrometry. The interactions between SLU7 and its binding site on circCAPG were validated by RIP-qPCR experiments.
resultsIn both TNBC clinical samples and cell lines, the expression level of circCAPG was identified to be higher compared with normal ones and positively correlated with the overall survival (n = 132) in a 10-year follow-up study, in which the area under the curve of receiver operating characteristic was 0.8723 with 100% specificity and 80% sensitivity. In addition, we found that circCAPG knockdown (KD) significantly inhibited the growth of TNBC organoids. Intriguingly, circCAPG can be translated into a polypeptide named CAPG-171aa which promotes tumor growh by disrupting the binding of serine/threonine kinase 38 (STK38) to SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1) and thereby preventing MEKK2 ubiquitination and proteasomal degradation. Furthermore, we found that SLU7 Homolog- Splicing Factor (SLU7) can regulate the bio-generation of circCAPG through binding to the flanking Alu sequences of circRNA transcripts.
conclusionscircCAPG significantly enhances the proliferation and metastasis of TNBC cells by encoding a novel polypeptide CAPG-171aa and afterwards activates MEKK2-MEK1/2-ERK1/2 pathway. Additionally, the formation of circCAPG is found to be mediated by SLU7. The present study provides innovative insight into the role of protein-coding circRNAs CAPG-171aa in TNBC, and its capacity to serve as a promising prognostic biomarker and potential therapeutic target in TNBC.
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