Abstract 971: A novel long noncoding RNA, onco-lncRNA 230, induces apoptosis and invasion in lung squamous cell carcinoma

Abstract

Abstract Long non-coding RNAs (lncRNAs) are RNAs that are longer than 200 base pairs and do not translate into proteins but have been shown to play roles in all aspects of biological regulation. LncRNAs have also been shown to regulate gene expression including chromatin organization, transcriptional regulation, and post-transcriptional control. In addition, they are now emerging to be important players in our understanding of cancer and have been shown to promote tumorigenesis. However, the mechanisms driving the advancement of tumor progression to metastasis is poorly understood. To identify lncRNAs critical to tumorigenesis, our lab conducted a pan-cancer analysis of normal and primary tumor tissues from The Cancer Genome Atlas to discover lncRNAs that are commonly altered across cancer types, which we termed ‘onco-lncRNAs’. During our analysis, we discovered a novel unannotated onco-lncRNA, onco-lncRNA-230, that was significantly up regulated in head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) tumors relative to matched adjacent normal tissues, when available. We chose to focus on onco-lncRNA-230 as it displayed more than seven fold increase in LUAD and more than thirty seven fold change in LUSC tumors relative to adjacent normal. First, we validated this finding by quantitative PCR which revealed greater than a two fold enrichment of onco-lncRNA-230 expression in two out of seven LUAD and all six LUSC cells lines compared to a normal lung cell line. Because we observed the greatest increase in expression in HCC95 LUSC cells, we next sought to determine if modulating the expression of onco-lncRNA-230 promotes oncogenic phenotypes. Silencing of onco-lncRNA-230 in HCC95 cells did not change cellular proliferation but significantly increased apoptosis. Furthermore, silencing onco-lncRNA-230 resulted in a decrease in cellular invasion by transwell assay. Taken together, this represents the first study reporting that onco-lncRNA-230 is dysregulated in multiple cancer types, significantly up-regulated in lung cancer patient samples and lung cancer cell lines, and confers oncogenic phenotypes. Moving forward, we intend to explore how onco-lncRNA-230 mechanistically promotes lung cancer with the objective of utilizing onco-lncRNA-230 as a novel cancer diagnostic and therapy. Citation Format: Cynthia Y. Tang, Jessica M. Silva-Fisher, Ha X. Dang, Nicole M. White, Christopher A. Maher. A novel long noncoding RNA, onco-lncRNA 230, induces apoptosis and invasion in lung squamous cell carcinoma. [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 971.