The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer

Abstract The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cance...

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Autores principales:	Zhenbo Tu, Johannes Schmoellerl, Odette Mariani, Yurong Zheng, Yi Hu, Anne Vincent-Salomon, Antoine E. Karnoub
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/eb5b212410734bcb9411cb9cb050eda5
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spelling	oai:doaj.org-article:eb5b212410734bcb9411cb9cb050eda52021-12-02T15:02:54ZThe LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer10.1038/s41523-021-00259-z2374-4677https://doaj.org/article/eb5b212410734bcb9411cb9cb050eda52021-05-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00259-zhttps://doaj.org/toc/2374-4677Abstract The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.Zhenbo TuJohannes SchmoellerlOdette MarianiYurong ZhengYi HuAnne Vincent-SalomonAntoine E. KarnoubNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zhenbo Tu Johannes Schmoellerl Odette Mariani Yurong Zheng Yi Hu Anne Vincent-Salomon Antoine E. Karnoub The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
description	Abstract The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.
format	article
author	Zhenbo Tu Johannes Schmoellerl Odette Mariani Yurong Zheng Yi Hu Anne Vincent-Salomon Antoine E. Karnoub
author_facet	Zhenbo Tu Johannes Schmoellerl Odette Mariani Yurong Zheng Yi Hu Anne Vincent-Salomon Antoine E. Karnoub
author_sort	Zhenbo Tu
title	The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
title_short	The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
title_full	The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
title_fullStr	The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
title_full_unstemmed	The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
title_sort	linc01119-socs5 axis as a critical theranostic in triple-negative breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eb5b212410734bcb9411cb9cb050eda5
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The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer

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