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This study reanalyzes circRNA expression datasets from TNBC and identifies circCAPG for mechanistic investigation. CAPG-171aa, translated from circCAPG, enhances TNBC cell proliferation and metastasis by disrupting STK38 binding to SMURF1, preventing MEKK2 ubiquitination and proteasomal degradation, while SLU7 mediates circCAPG biogenesis.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-novel-polypeptide-capg-171aa-encoded-by-circcapg-plays-a-critical-role-in-triple-negative-breast-cancer/379020/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-novel-polypeptide-capg-171aa-encoded-by-circcapg-plays-a-critical-role-in-triple-negative-breast-cancer/379020.png","ImageObject",300,407,{"name":92,"@type":93},"Jacob","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address in triple-negative breast cancer (TNBC)?","Question",{"text":112,"@type":113},"TNBC is challenging to treat because of its heterogeneity and the lack of well-defined molecular targets. The study aims to clarify how protein-coding circRNAs contribute to TNBC etiology and carcinogenesis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the researchers identify the function of circCAPG and its encoded polypeptide?",{"text":117,"@type":113},"They reanalyzed circRNA expression data, selected circCAPG, and used experiments such as mass spectrometry and dual-luciferase reporter assays. Functional assays assessed proliferation, apoptosis, and metastasis in TNBC organoids and nude mice.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism explains how CAPG-171aa promotes TNBC progression?",{"text":121,"@type":113},"CAPG-171aa promotes tumor growth by disrupting the binding of STK38 to SMURF1, thereby preventing MEKK2 ubiquitination and proteasomal degradation. The study also reports activation of the MEKK2-MEK1/2-ERK1/2 pathway and regulation of circCAPG formation by SLU7.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},379020,1790330876,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31},962084931830,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Song et al. Molecular Cancer (2023) 22:104 Molecular Cancer  \n[https://doi.org/10.1186/s12943-023-01806-x](https://doi.org/10.1186/s12943-023-01806-x)  \nRESEARCH Open Access  \nA novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triplenegative breast cancer  \nRunjie Song1†, Peilan Guo1†, Xin Ren1†, Lijun Zhou1, Peng Li 1, Nafis A Rahman2,3, Sławomir Wołczyński3, Xiru Li4, Yanjun Zhang4, Mei Liu5, Jiali Liu 1 and Xiangdong Li 1,3*  \nAbstract  \nBackground 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 ofTNBC.  \nMethods CircRNA expression data inTNBC (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 inTNBC was verified by immunoprecipitation analyses and mass spectrometry. The interactions between SLU7 and its binding site oncircCAPG 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 ofTNBC 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 ofTNBC cells by encoding a novel polypeptide CAPG-171aa and afterwards activates MEKK2-MEK1/2-ERK1/2 pathway. Additionally, the formation ofcircCAPG is found to be mediated by SLU7. The present study provides innovative insight into the role of protein-  \n†Runjie Song, Peilan Guo and Xin Ren contributed equally.  \n*Correspondence: Xiangdong Li [xiangdongli68@126.com](xiangdongli68@126.com)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The)[. The](http://creativecommons.org/licenses/by/4.0/. The)[ ](http://creativecommons.org/licenses/by/4.0/. The)Creative Commons Public Domain ","cbCaikgAo7k7zBxf","https://ap.wps.com/l/cbCaikgAo7k7zBxf","pdf",15423094,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n## Keywords\n## Background","[{\"question\":\"What problem does the study address in triple-negative breast cancer (TNBC)?\",\"answer\":\"TNBC is challenging to treat because of its heterogeneity and the lack of well-defined molecular targets. The study aims to clarify how protein-coding circRNAs contribute to TNBC etiology and carcinogenesis.\"},{\"question\":\"How did the researchers identify the function of circCAPG and its encoded polypeptide?\",\"answer\":\"They reanalyzed circRNA expression data, selected circCAPG, and used experiments such as mass spectrometry and dual-luciferase reporter assays. Functional assays assessed proliferation, apoptosis, and metastasis in TNBC organoids and nude mice.\"},{\"question\":\"What mechanism explains how CAPG-171aa promotes TNBC progression?\",\"answer\":\"CAPG-171aa promotes tumor growth by disrupting the binding of STK38 to SMURF1, thereby preventing MEKK2 ubiquitination and proteasomal degradation. The study also reports activation of the MEKK2-MEK1/2-ERK1/2 pathway and regulation of circCAPG formation by SLU7.\"}]","A novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triple-negative breast cancer | PDF",1790233730]