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This study investigates how the transcription factor ETV1, regulated by m6A methylation, influences MM progression and TAM M2 polarization. Gene-expression analyses and functional assays show that ETV1 upregulation worsens prognosis, enhances MM proliferation, and drives M2 polarization, linking METTL3-mediated m6A modification to ETV1-dependent RBMS1 transcriptional activation.",{"@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/m6a-methylation-modified-etv1-drives-multiple-myeloma-progression-and-m2-polarization-of-tumor-associated-macrophage-through-transcriptional-activation-of-rbms1/359111/",{"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/m6a-methylation-modified-etv1-drives-multiple-myeloma-progression-and-m2-polarization-of-tumor-associated-macrophage-through-transcriptional-activation-of-rbms1/359111.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role do ETV1 and m6A methylation play in multiple myeloma progression?","Question",{"text":112,"@type":113},"ETV1 is significantly upregulated in MM and is associated with poor prognosis. The study links METTL3-mediated m6A methylation to increased ETV1 expression, which promotes MM cell proliferation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does ETV1 affect tumor-associated macrophages in the MM microenvironment?",{"text":117,"@type":113},"Ectopic ETV1 expression enhances M2 polarization of TAMs, while ETV1 knockdown shows the opposite effect. This supports a tumor-permissive, immunosuppressive state.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism connects ETV1 to the pro-tumor effects observed in vivo?",{"text":121,"@type":113},"The findings show that ETV1 transcriptionally activates RBMS1. RBMS1 knockdown abrogates the pro-tumorigenic effects driven by ETV1 overexpression.","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},359111,1790167275,{"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":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","Liu et al. Journal of Translational Medicine (2026) 24:394  \n[https://doi.org/10.1186/s12967-026-07799-7](https://doi.org/10.1186/s12967-026-07799-7)  \nJournal of Translational Medicine  \nRESEARCH Open Access  \nm6A methylation-modified ETV1 drives  multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1  \nYan Liu1†, Yueqi Geng1†, Boyang Zheng1, Aijia Zhang2, Kerou Yang2, Yinling Mao2* and Li Jiang1*  \nAbstract  \nBackground Multiple myeloma (MM) is an incurable tumor characterized by the clonal expansion of  \nmalignant plasma cells in the bone marrow. Tumor-associated macrophages (TAMs) play a crucial role in the  \nMM microenvironment by promoting plasma cell survival and conferring therapy resistance. ETV1 (E-twenty-six transformation-specific variant 1) is a transcription factor that has been proven to be an oncogenic driver in various cancers, but its functional role and the potential mechanisms in MM remain poorly understood.  \nMethods Gene expression profiles were analyzed in bone marrow plasma cells from three healthy and 45 MM samples obtained from the GSE125361 dataset. Cell growth was assessed using CCK-8 and colony formation  \nassays. Macrophage phenotypes were characterized by flow cytometry, and TAM infiltration was evaluated via immunofluorescence double staining. Tumor development was detected by in vivo fluorescence imaging system. Transcriptional activity was examined using luciferase reporter and chromatin immunoprecipitation (ChIP) assays. The N6-Methyladenosine (m6A) modification levels of ETV1 in MM cells were detected by m6A RNA immunoprecipitation followed by qPCR (m6A RIP-qPCR), and the interaction between ETV1 mRNA and METTL3 (methyltransferase-like 3) was evaluated using RIP-PCR.  \nResults Bioinformatics analysis revealed that ETV1 was significantly upregulated in MM and associated with poor prognosis of MM patients. Gain-of-function and loss-of-function experiments demonstrated that ETV1 overexpression enhanced MM cell proliferation and M2 polarization ofTAMs both in vitro and in vivo, whereas ETV1 knockdown exerted the opposite effects. Mechanistically, we confirmed that METTL3 upregulated ETV1 expression by enhancing its m6A methylation modification. Furthermore, ETV1 transcriptionally activated RBMS1 (RNA-binding motif,  \nsingle-stranded-interacting protein 1), and RBMS1 knockdown abrogated the pro-tumorigenic effects of ETV1 overexpression.  \n†Yan Liu and Yueqi Geng contributed equally to this work.  \n*Correspondence: Yinling Mao [830216@hrbmu.edu.cn](830216@hrbmu.edu.cn)[ ](830216@hrbmu.edu.cn)Li Jiang [601935@hrbmu.edu.cn](601935@hrbmu.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.)  \nLiu et al. Journal of Translational Medicine (2026) 24:394 Page 2 of 16  \nConclusions Thes","cbCaiutHQwaN6iLG","https://ap.wps.com/l/cbCaiutHQwaN6iLG","pdf",3726844,16,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What role do ETV1 and m6A methylation play in multiple myeloma progression?\",\"answer\":\"ETV1 is significantly upregulated in MM and is associated with poor prognosis. The study links METTL3-mediated m6A methylation to increased ETV1 expression, which promotes MM cell proliferation.\"},{\"question\":\"How does ETV1 affect tumor-associated macrophages in the MM microenvironment?\",\"answer\":\"Ectopic ETV1 expression enhances M2 polarization of TAMs, while ETV1 knockdown shows the opposite effect. This supports a tumor-permissive, immunosuppressive state.\"},{\"question\":\"What mechanism connects ETV1 to the pro-tumor effects observed in vivo?\",\"answer\":\"The findings show that ETV1 transcriptionally activates RBMS1. RBMS1 knockdown abrogates the pro-tumorigenic effects driven by ETV1 overexpression.\"}]","m6A methylation-modified ETV1 drives multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1 | PDF",1790136138]