The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer.
The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer.
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DOI：
10.1038/s41523-021-00259-z
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发表时间：
2021-05-31
影响因子：
5.9
通讯作者：
Karnoub AE
中科院分区：
文献类型：
--
作者：
Tu Z;Schmoellerl J;Mariani O;Zheng Y;Hu Y;Vincent-Salomon A;Karnoub AE
三阴性乳腺癌（TNBC）的发展受到某些肿瘤微环境相关细胞（称为间充质干细胞/基质细胞（MSC））的关键调控，我们和其他人已经表明，通过激活邻近癌细胞中的促恶性信号传导，促进TNBC进展。这些级联的表征将使我们更好地理解TNBC生物学，并带来消除与晚期疾病相关的发病率和死亡率的治疗方法。在这里，我们专注于称为长非编码RNA或lncRNA的新兴RNA类别，并利用MSC支持的TNBC进展模型来鉴定与TNBC发病机制功能相关的特定家族成员。事实上，尽管已经描述了一些在TNBC中发挥功能性作用，但lncRNA作为肿瘤微环境驱动的TNBC发展的介体的活性仍有待充分探索。我们报道了MSC刺激TNBC细胞中LINC 01119的稳健表达，这反过来诱导细胞因子信号传导抑制因子5（SOCS 5），导致癌细胞生长和肿瘤发生加速。我们发现LINC 01119和SOCS 5在多个乳腺癌基因组中表现出紧密的相关性，并且它们在TNBC患者队列中高度富集。重要的是，我们提出的证据表明LINC 01119-SOCS 5轴代表了TNBC患者不良结局的有力预后指标，并证明其抑制严重损害癌细胞生长。总之，我们的研究结果将LINC 01119确定为TNBC发展的主要驱动因素，并描述了在晚期TNBC管理中具有潜在翻译效用的重要非编码RNA治疗诊断学，这是一类最需要有效和靶向治疗的肿瘤。
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.
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影响因子：
23.9
作者：
Cuiffo, Benjamin G.;Campagne, Antoine;Kamoub, Antoine E.
通讯作者：
Kamoub, Antoine E.
影响因子：
45.3
作者：
Bardia, Aditya;Mayer, Ingrid A.;Vahdat, Linda T.
通讯作者：
Vahdat, Linda T.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
DOI：
10.1016/j.hbpd.2020.02.011
发表时间：
2020-12-01
影响因子：
3.3
作者：
Bi, Hua-Qiang;Li, Zhong-Hui;Zhang, Hui
通讯作者：
Zhang, Hui
DOI：
10.15252/embj.201489385
发表时间：
2014-11-03
期刊：
The EMBO journal
影响因子：
--
作者：
Hong X;Nguyen HT;Chen Q;Zhang R;Hagman Z;Voorhoeve PM;Cohen SM
通讯作者：
Cohen SM