Abstract 3502: RNAi screen identified novel long non-coding RNAs involved in cell growth control, migration, and invasion

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer often associated with poor prognosis. Owing to the lack of therapeutic targets, patients with TNBC tend to rely on standard chemotherapy; however, chemo-resistance often develops in TNBC as a result of deregulated cell death control like in many other tumors. Long non-coding RNAs (lncRNAs) are transcripts longer than 200bp and have little or no protein-coding capacity. Although once considered as transcriptional noise, significant numbers of lncRNAs are now known as modulators of protein expression and functions and are implicated in a range of developmental processes and diseases. As many of them influence oncogenes and tumor suppressors in cancer, they represent excellent biomarkers as well as potential targets for therapy. In order to gain more insight on cell death regulation and to seek potential targets for TNBC, we employed an RNAi screen targeting 2231 lncRNAs in MDA-MB-231 TNBC cells. By using changes in cell metabolic activity (MTT assay) as readouts for primary screen and changes in cell number as confirmation, our unbiased screen identified two novel lncRNAs that drastically reduced cell proliferation when depleted. In addition to cell growth, the two lncRNAs also contribute to cancer cell migration and invasion. Interestingly, our gene profiling analyses and RNA immunoprecipitation studies show the two lncRNAs are involved in signaling cascades known to promote mammary tumorigenesis including EGF and β-catenin. We are now trying to delineate the detailed molecular mechanism(s) by which the two lncRNAs contribute to TNBC tumorigenesis. Together, our current results suggest a possibility for the two novel lncRNAs as drug targets in triple-negative breast cancer. Citation Format: Tse-Chun Kuo, Sheng-Chieh Hsu, Hui-Ju Chou, Pei-Shan Li, Szu-Huei Wu, Yen-Ling Yu, Jen-Shin Song, Hsing-Jien Kung. RNAi screen identified novel long non-coding RNAs involved in cell growth control, migration, and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3502. doi:10.1158/1538-7445.AM2017-3502