Abstract 3498: Characterization of a novel metastatic lung cancer associated lncRNA

Abstract

Abstract Lung cancer is the leading cause of death worldwide with the majority of patients presenting with metastasis and moreover, developing resistance to current treatments. One promising therapeutic area is the novel class of long noncoding RNAs (lncRNAs). While emerging evidence implicates them in cancer, lncRNA biology is still largely unexplored in tumor metastasis. To elucidate the function of lncRNAs in lung cancer, our lab used transcriptome sequencing (RNA-Seq) to discover 120 long non-coding RNAs (lncRNAs) that are enriched in metastatic tumors compared to their corresponding primary lung tumors, which we have named Metastasis Associated Lung cancer LncRNAs (MALLs). Notably, metastatic tumors were enriched for differentially expressed protein-coding genes targeted by Polycomb Repressive Complex 2 (PRC2). In lung cancer studies show that the catalytic subunit of PRC2, EZH2 (an H3K27 methylase), is overexpressed, associates with poor prognosis, promotes tumor progression, and epigenetically represses genes to promote metastasis. Specifically, we have found MALL-1 to be (i) highly up-regulated in lung cancer; (ii) promotes proliferation and migration/invasion, hallmarks of oncogenic phenotypes; (iii) binds to EZH2; and (iv) cooperatively represses well-known PRC2 target genes associated with metastasis in patients. Further, we found MALL-1 to be altered in multiple solid tumors thus suggesting a critical conserved oncogenic role of MALL-1 in solid tumor progression. We believe MALL-1 promotes aggressive disease through its interactions with, and recruitment of the PRC2 complex to chromatin, to epigenetically modify genes associated with metastasis. Citation Format: Nicole M. White, Emily B. Rozycki, Ha X. Dang, Christopher A. Maher. Characterization of a novel metastatic lung cancer associated lncRNA [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 3498. doi:10.1158/1538-7445.AM2017-3498