A novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triple-negative breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37408008", "kind": "science-record", "revision": 3, "content_hash": "sha256:6b2369651c960ab35152a1cb5ef2d6c728c192a36915462a2fa76b1a9ccdc770", "created_at": "2026-11-01T19:02:10Z", "updated_at": "2026-11-01T21:31:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triple-negative breast cancer.", "doi": "10.1186/s12943-023-01806-x", "pmid": "37408008", "authors": ["Runjie Song", "Peilan Guo", "Xin Ren", "Lijun Zhou", "Peng Li", "Nafis A Rahman", "Sławomir Wołczyński", "Xiru Li", "Yanjun Zhang", "Mei Liu", "Jiali Liu", "Xiangdong Li"], "journal": "Molecular cancer", "year": 2023, "abstract": "BACKGROUND: The 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.\nMETHODS: CircRNA 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.\nRESULTS: In 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.\nCONCLUSIONS: circCAPG 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.", "claims": [{"id": "claim-method", "statement": "Two-tailed Student’s t-test was performed to calculate statistical significance with GraphPad Prism 8 (version 8.0.1, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37408008", "locator": "sections[22] \"Statistical analysis\" paragraph 2", "quote": "Two-tailed Student’s t-test was performed to calculate statistical significance with GraphPad Prism 8 (version 8.0.1, USA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37408008", "locator": "sections[41] \"notes\" paragraph 1", "quote": "The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "circCAPG 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.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37408008", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "circCAPG 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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "circCAPG 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.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37408008"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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RESULTS: In both TNBC clinical"], "order_basis": "paper_text_order:1029", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["itivity. In addition, we found that circCAPG knockdown (KD) significantly inhibited the growth of T"], "order_basis": "paper_text_order:1442", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Solarbio, China) and growth supplements. All cell lines were cultured in 5% CO2 at 37 °C in a humidified atmospher", ". HEK293T, Hs578T, MCF7, and T47D cells were cultured with Dulbecco’s modified Eagle’s medium (DMEM, Gi", "upplemented with 10% FBS. ZR-75-1 cells were cultured with Minimum Essential Medium (KeyGEN, KGM41500N-", "and growth supplements. All cell lines were cultured in 5% CO2 at 37 °C in a humidified atmosphere."], "order_basis": "paper_text_order:3299", "id": "assay:5"}]}