Abstract 3702: A lineage-specific lncRNA driven by Foxa1 associated super enhancer promotes tumor growth through interacting YBX1

Abstract

Abstract Lineage-specific expression of genes plays important roles in tumorigenesis. It has been suggested that lncRNAs tend to be more lineage-specifically expressed than protein-coding genes. However, the regulation and role of lineage-specific lncRNAs remains largely unknown. In this study, we reported a lncRNA DSCAM-AS1 that specifically expressed in lung adenocarcinoma and luminal breast cancer. The expression of DSCAM-AS1 was regulated by two super enhancer clusters driven by Foxa1. Foxa1 can directly bind to promoter of DSCAM-AS1. In breast cancer, DSCAM-AS1 was also transcriptionally regulated by ERα, which formed complex with Foxa1. Higher expression of DSCAM-AS1 was associated with poor poor prognosis in both lung adenocarcinoma and luminal breast cancer patients. Silencing or knock-out of DSCAM-AS1 significantly reduce the growth of lung adenocarcinoma and luminal breast cancer cells. We observed silencing or knock-out of DSCAM-AS1 could reduce the expression of Foxa1 in lung adenocarcinoma and breast cancer cells. We also found a significant decrease of ERα expression after silencing or knock-out of DSCAM-AS1 in luminal breast cancer cells. Mechanistically, we found DSCAM-AS1 could interact with YBX1 and enhance recruitment of YBX1 at the promoter region of Foxa1 and ERα. DSCAM-AS1 could form a positive feedback loop with Foxa1 and ERα. Our findings may provide another regulatory loop: Foxa1 and ERα drive expression of super enhancer associated lncRNA DSCAM-AS1 and form a positive feedback loop with it, which play important roles in maintaining cancer cell identity and function. Citation Format: Yin Zhang, Yong-xin Huang, Dan-lan Wang, Hai-yan Yan, Yin Dong. A lineage-specific lncRNA driven by Foxa1 associated super enhancer promotes tumor growth through interacting YBX1 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3702.