Shuo Feng, Yaping Wang, Ran Ren, Xiaotong Wang, Lu Han
{"title":"高表达的formin-2可通过免疫抑制巨噬细胞促进卵巢癌化疗耐药","authors":"Shuo Feng, Yaping Wang, Ran Ren, Xiaotong Wang, Lu Han","doi":"10.1007/s10142-025-01766-z","DOIUrl":null,"url":null,"abstract":"<div><p>Ovarian cancer (OC) remains a major threat to women’s health, with chemoresistance driven by the immunosuppressive tumor microenvironment. Formin-2 (FMN2), a cytoskeletal regulator, was investigated for its role in OC chemoresistance and macrophage polarization. Bioinformatics analysis identified high FMN2 expression in chemotherapy-resistant OC cell lines, validated experimentally. Stable FMN2 knockdown cell lines were generated via lentiviral transfection. Functional assays revealed that FMN2 overexpression conferred chemoresistance in vitro and in vivo and promoted M2 macrophage polarization via the CCL2/JAK2/STAT3 pathway. Co-culture with M2 macrophages enhanced cisplatin (DDP) resistance in OC cells, mediated by CXCL1 secretion, which activated the epithelial-mesenchymal transition (EMT) pathway. Clinically, FMN2 levels correlated with CCL2 and CD206 (M2 marker) in platinum-resistant patients, and high FMN2, CCL2, or CD206 expression predicted poorer overall and disease-free survival. This study identifies FMN2 as a key mediator of chemoresistance and immune evasion in OC, proposing FMN2-CCL2-CD206 signaling and macrophage-derived CXCL1 as therapeutic targets and prognostic markers for chemotherapy response.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High expression of formin-2 can promote ovarian cancer chemoresistance via immunosuppressive macrophages\",\"authors\":\"Shuo Feng, Yaping Wang, Ran Ren, Xiaotong Wang, Lu Han\",\"doi\":\"10.1007/s10142-025-01766-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Ovarian cancer (OC) remains a major threat to women’s health, with chemoresistance driven by the immunosuppressive tumor microenvironment. Formin-2 (FMN2), a cytoskeletal regulator, was investigated for its role in OC chemoresistance and macrophage polarization. Bioinformatics analysis identified high FMN2 expression in chemotherapy-resistant OC cell lines, validated experimentally. Stable FMN2 knockdown cell lines were generated via lentiviral transfection. Functional assays revealed that FMN2 overexpression conferred chemoresistance in vitro and in vivo and promoted M2 macrophage polarization via the CCL2/JAK2/STAT3 pathway. Co-culture with M2 macrophages enhanced cisplatin (DDP) resistance in OC cells, mediated by CXCL1 secretion, which activated the epithelial-mesenchymal transition (EMT) pathway. Clinically, FMN2 levels correlated with CCL2 and CD206 (M2 marker) in platinum-resistant patients, and high FMN2, CCL2, or CD206 expression predicted poorer overall and disease-free survival. This study identifies FMN2 as a key mediator of chemoresistance and immune evasion in OC, proposing FMN2-CCL2-CD206 signaling and macrophage-derived CXCL1 as therapeutic targets and prognostic markers for chemotherapy response.</p></div>\",\"PeriodicalId\":574,\"journal\":{\"name\":\"Functional & Integrative Genomics\",\"volume\":\"26 1\",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Functional & Integrative Genomics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10142-025-01766-z\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Functional & Integrative Genomics","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10142-025-01766-z","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
High expression of formin-2 can promote ovarian cancer chemoresistance via immunosuppressive macrophages
Ovarian cancer (OC) remains a major threat to women’s health, with chemoresistance driven by the immunosuppressive tumor microenvironment. Formin-2 (FMN2), a cytoskeletal regulator, was investigated for its role in OC chemoresistance and macrophage polarization. Bioinformatics analysis identified high FMN2 expression in chemotherapy-resistant OC cell lines, validated experimentally. Stable FMN2 knockdown cell lines were generated via lentiviral transfection. Functional assays revealed that FMN2 overexpression conferred chemoresistance in vitro and in vivo and promoted M2 macrophage polarization via the CCL2/JAK2/STAT3 pathway. Co-culture with M2 macrophages enhanced cisplatin (DDP) resistance in OC cells, mediated by CXCL1 secretion, which activated the epithelial-mesenchymal transition (EMT) pathway. Clinically, FMN2 levels correlated with CCL2 and CD206 (M2 marker) in platinum-resistant patients, and high FMN2, CCL2, or CD206 expression predicted poorer overall and disease-free survival. This study identifies FMN2 as a key mediator of chemoresistance and immune evasion in OC, proposing FMN2-CCL2-CD206 signaling and macrophage-derived CXCL1 as therapeutic targets and prognostic markers for chemotherapy response.
期刊介绍：
Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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