Abstract
Abstract Background: Long non-coding RNAs (LINCs) are an emerging class of molecules in cancer diagnosis and prognosis. The number of LINCs exceeds the number of protein-coding genes and their role in breast cancer is largely unknown. Methods: In this study we used non-adherent growing tumor spheres (“mammospheres”) as a model system to identify tumor-sphere associated (TSA) gene expression patterns. We used microarrays to profile different breast cancer cell lines and selected the most up/down-regulated differentially expressed genes by RT-PCR. Clinical correlations including survival analysis of almost 900 breast cancer patients in two independent cohorts and experimental evaluation of the biological function were done. Results: Among several TSA-genes, one novel not previously reported LINC, (that we termed TSA-LINC2) was significantly up-regulated in mammospheres (up to 50 fold, p<0.05). In patient samples, TSA-LINC2 was significantly up-regulated in cancer tissue compared to normal breast tissue, and high expression was associated with poor survival in different molecular breast cancer subtypes (p<0.05). Knock-down experiments of TSA-LINC2 in a panel of breast cancer cell lines led to significantly altered cellular growth, anchorage-independent growth and mammosphere formation in triple negative (p<0.05). Molecular profiling with gene expression arrays shows that TSA-LINC2 regulates cell cycle-associated genes. Conclusion: This novel long non-coding RNAis involved in breast cancer progression and might be useful as a prognostic marker in breast cancer patients. Citation Format: Martin Pichler, Stefanie Cerk, Verena Stiegelbauer, Daniela Schwarzenbacher, Hui Ling. A novel long non-coding RNA, TSA-LINC2, regulates cellular growth and is associated with poor prognosis in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 988.
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