Abstract 157: LncRNA ANRIL indicates a potential prognostic biomarker in gastric cancer and promotes tumor growth by silencing of miR-99a/miR-449a

Abstract

Abstract Long noncoding RNAs are involved in several kinds of cancers. Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in human gastric cancer (GC) tissues. In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with higher TNM stages (P = 0.041) and larger tumor sizes (P = 0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (OS) (P = 0.036). Further experiments revealed that the knockdown of ANRIL significantly repressed the proliferation of GC cell lines both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is partly due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets_mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation. To our knowledge, this is the first report which showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level. Our results suggest that ANRIL, as a growth regulator, may serve as a potential prognostic biomarker and target for new therapies in human GC. Citation Format: Zhi Xu, Jinfei Chen, John M. Luk, Wei De. LncRNA ANRIL indicates a potential prognostic biomarker in gastric cancer and promotes tumor growth by silencing of miR-99a/miR-449a. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 157. doi:10.1158/1538-7445.AM2015-157