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.