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

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 promoted TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades will better our understanding of TNBC biology, and stands to bring about therapeutics that can eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of non-coding 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 for lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulated robust expression of LINC01119 in TNBC cells, which in turn induced suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibited tight correlation across multiple breast cancer gene sets and that they were highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis served as a powerful prognostic indicator of adverse outcome in TNBC patients, and we demonstrate that its repression severely impaired 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.