{"title":"通过POSTN/Hippo/YAP轴调节巨噬细胞M2极化，肿瘤源性细胞外囊泡封闭lncRNA MALAT1对三阴性乳腺癌的增殖、侵袭和转移的影响","authors":"","doi":"10.1016/j.tranon.2024.102076","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated the mechanism of TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis.</p></div><div><h3>Methods</h3><p>BC-associated targeted EV-derived lncRNAs were screened. Tumor tissues/tissues adjacent to cancer of TNBC patients, and blood samples of all subjects were collected. MALAT1/POSTN mRNA levels in tumor tissues/tissues adjacent to cancer, and MALAT1 expression in EVs and its correlation with TNBC patient overall survival were assessed by RT-qPCR/Kaplan-Meier survival analysis/log-rank test. TNBC patient M2 infiltration was detected by flow cytometry. MALAT1/POSTN levels in EVs/macrophages were regulated by transfection. Hippo/YAP activation was determined by Western blot. Nude mouse xenograft model was established and metastasis was detected by H&E staining.</p></div><div><h3>Results</h3><p>MALAT1/POSTN were up-regulated and correlated with M2 infiltration/poor prognosis in TNBC patients. TNBC-derived EVs induced M2 polarization. MALAT1 was highly expressed in TNBC-derived EVs and could be transferred to macrophages via EVs to induce M2 polarization. POSTN overexpression diminished the inhibitory effect of MALAT1 knockdown on M2 markers. EVs activated the Hippo/YAP pathway in macrophages. The Hippo/YAP pathway inhibition abrogated the effect of POSTN overexpression on M2 marker expression. TNBC-EV-derived MALAT1 facilitated M2 polarization, and thus promoting occurrence and metastasis of TNBC <em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Conclusions</h3><p>TNBC-EV-derived MALAT1 activated the Hippo/YAP axis by up-regulating POSTN, thereby inducing M2 polarization to promote TNBC occurrence and metastasis <em>in vivo</em>.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002031/pdfft?md5=6f57ccde0c22a156c7d194a23faa9804&pid=1-s2.0-S1936523324002031-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Effect of tumor-derived extracellular vesicle-shuttled lncRNA MALAT1 on proliferation, invasion and metastasis of triple-negative breast cancer by regulating macrophage M2 polarization via the POSTN/Hippo/YAP axis\",\"authors\":\"\",\"doi\":\"10.1016/j.tranon.2024.102076\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><p>Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated the mechanism of TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis.</p></div><div><h3>Methods</h3><p>BC-associated targeted EV-derived lncRNAs were screened. Tumor tissues/tissues adjacent to cancer of TNBC patients, and blood samples of all subjects were collected. MALAT1/POSTN mRNA levels in tumor tissues/tissues adjacent to cancer, and MALAT1 expression in EVs and its correlation with TNBC patient overall survival were assessed by RT-qPCR/Kaplan-Meier survival analysis/log-rank test. TNBC patient M2 infiltration was detected by flow cytometry. MALAT1/POSTN levels in EVs/macrophages were regulated by transfection. Hippo/YAP activation was determined by Western blot. Nude mouse xenograft model was established and metastasis was detected by H&E staining.</p></div><div><h3>Results</h3><p>MALAT1/POSTN were up-regulated and correlated with M2 infiltration/poor prognosis in TNBC patients. TNBC-derived EVs induced M2 polarization. MALAT1 was highly expressed in TNBC-derived EVs and could be transferred to macrophages via EVs to induce M2 polarization. POSTN overexpression diminished the inhibitory effect of MALAT1 knockdown on M2 markers. EVs activated the Hippo/YAP pathway in macrophages. The Hippo/YAP pathway inhibition abrogated the effect of POSTN overexpression on M2 marker expression. TNBC-EV-derived MALAT1 facilitated M2 polarization, and thus promoting occurrence and metastasis of TNBC <em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Conclusions</h3><p>TNBC-EV-derived MALAT1 activated the Hippo/YAP axis by up-regulating POSTN, thereby inducing M2 polarization to promote TNBC occurrence and metastasis <em>in vivo</em>.</p></div>\",\"PeriodicalId\":48975,\"journal\":{\"name\":\"Translational Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1936523324002031/pdfft?md5=6f57ccde0c22a156c7d194a23faa9804&pid=1-s2.0-S1936523324002031-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1936523324002031\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1936523324002031","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
摘要
目的三阴性乳腺癌（TNBC）是乳腺癌（BC）中最致命的亚型。肿瘤衍生的细胞外囊泡（EVs）通过促进M2极化引发肿瘤进展。一些lncRNA可被包裹到EVs中进行细胞间通信。在此，我们研究了TNBC衍生的EV-shuttled lncRNA MALAT1对巨噬细胞极化/肿瘤发生的机制。收集 TNBC 患者的肿瘤组织/癌旁组织以及所有受试者的血液样本。通过RT-qPCR/Kaplan-Meier生存分析/log-rank检验评估了肿瘤组织/癌症邻近组织中的MALAT1/POSTN mRNA水平、EV中的MALAT1表达及其与TNBC患者总生存期的相关性。通过流式细胞术检测TNBC患者的M2浸润。通过转染调节EVs/巨噬细胞中的MALAT1/POSTN水平。通过 Western 印迹检测 Hippo/YAP 激活情况。结果MALAT1/POSTN上调并与TNBC患者的M2浸润/预后不良相关。TNBC衍生的EV诱导M2极化。MALAT1在TNBC衍生的EVs中高表达，并可通过EVs转移到巨噬细胞中诱导M2极化。POSTN的过表达削弱了MALAT1敲除对M2标记物的抑制作用。EVs激活了巨噬细胞中的Hippo/YAP通路。抑制Hippo/YAP通路可减轻POSTN过表达对M2标记表达的影响。结论TNBC-EV衍生的MALAT1通过上调POSTN激活Hippo/YAP轴，从而诱导M2极化，促进TNBC在体内的发生和转移。
Effect of tumor-derived extracellular vesicle-shuttled lncRNA MALAT1 on proliferation, invasion and metastasis of triple-negative breast cancer by regulating macrophage M2 polarization via the POSTN/Hippo/YAP axis
Objectives
Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated the mechanism of TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis.
Methods
BC-associated targeted EV-derived lncRNAs were screened. Tumor tissues/tissues adjacent to cancer of TNBC patients, and blood samples of all subjects were collected. MALAT1/POSTN mRNA levels in tumor tissues/tissues adjacent to cancer, and MALAT1 expression in EVs and its correlation with TNBC patient overall survival were assessed by RT-qPCR/Kaplan-Meier survival analysis/log-rank test. TNBC patient M2 infiltration was detected by flow cytometry. MALAT1/POSTN levels in EVs/macrophages were regulated by transfection. Hippo/YAP activation was determined by Western blot. Nude mouse xenograft model was established and metastasis was detected by H&E staining.
Results
MALAT1/POSTN were up-regulated and correlated with M2 infiltration/poor prognosis in TNBC patients. TNBC-derived EVs induced M2 polarization. MALAT1 was highly expressed in TNBC-derived EVs and could be transferred to macrophages via EVs to induce M2 polarization. POSTN overexpression diminished the inhibitory effect of MALAT1 knockdown on M2 markers. EVs activated the Hippo/YAP pathway in macrophages. The Hippo/YAP pathway inhibition abrogated the effect of POSTN overexpression on M2 marker expression. TNBC-EV-derived MALAT1 facilitated M2 polarization, and thus promoting occurrence and metastasis of TNBC in vitro and in vivo.
Conclusions
TNBC-EV-derived MALAT1 activated the Hippo/YAP axis by up-regulating POSTN, thereby inducing M2 polarization to promote TNBC occurrence and metastasis in vivo.
期刊介绍：
Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
