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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.
Wang, Xuedong; Jian, Qiwei; Zhang, Ziyun; Gu, Juan; Wang, Xinping; Wang, Yueping.
Afiliación
  • Wang X; School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, 232001, China; Center for Precision Medicine, Anhui No.2 Provincial People's Hospital, Hefei, Anhui, 230041, China.
  • Jian Q; School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, 232001, China.
  • Zhang Z; Center for Precision Medicine, Anhui No.2 Provincial People's Hospital, Hefei, Anhui, 230041, China.
  • Gu J; Center for Precision Medicine, Anhui No.2 Provincial People's Hospital, Hefei, Anhui, 230041, China.
  • Wang X; School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, 232001, China.
  • Wang Y; Center for Precision Medicine, Anhui No.2 Provincial People's Hospital, Hefei, Anhui, 230041, China; Department of Molecular and Cellular Biology, University of Connecticut, Storrs, CT, 06269, USA. Electronic address: wy1005@126.com.
Transl Oncol ; 49: 102076, 2024 Nov.
Article en En | MEDLINE | ID: mdl-39222611
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos