Long non‐coding RNA NNT ‐ AS 1 sponges miR‐424/E2F1 to promote the tumorigenesis and cell cycle progression of gastric cancer

作者：Beibei Chen, Zhao Qingfang, Lulu Guan, Huifang Lv, Liangyu Bie, Jinxi Huang, Xiao‐Bing Chen · 发表于：Journal of Cellular and Molecular Medicine · 年份：2018 · DOI：10.1111/jcmm.13726 · 被引用次数：50 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、Circular RNAs in diseases

Long non-coding RNAs (lncRNAs) have been illustrated to function as important regulators in carcinogenesis and cancer progression. However, the roles of lncRNA NNT-AS1 in gastric cancer remain unclear. In the present study, we investigate the biological role of NNT-AS1 in gastric cancer tumorigenesis. Results revealed that NNT-AS1 expression level was significantly up-regulated in GC tissue and cell lines compared with adjacent normal tissue and normal cell lines. The ectopic overexpression of NNT-AS1 indicated the poor prognosis of GC patients. In vitro experiments validated that NNT-AS1 knockdown suppressed the proliferation and invasion ability and induced the GC cell cycle progression arrest at G0/G1 phase. In vivo xenograft assay, NNT-AS1 silencing decreased the tumour growth of GC cells. Bioinformatics online program predicted that miR-424 targeted the 3'-UTR of NNT-AS1. Luciferase reporter assay, RNA-immunoprecipitation (RIP) and RNA pull-down assay validated the molecular binding within NNT-AS1 and miR-424, therefore jointly forming the RNA-induced silencing complex (RISC). Moreover, E2F1 was verified to act as the target gene of NNT-AS1/miR-424, indicating the NNT-AS1/miR-424/E2F1 axis. In conclusion, our study indicates that NNT-AS1 sponges miR-424/E2F1 to facilitate GC tumorigenesis and cycle progress, revealing the oncogenic role of NNT-AS1 for GC.