Open AccessLong non‐coding RNA NNT ‐ AS 1 sponges miR‐424/E2F1 to promote the tumorigenesis and cell cycle progression of gastric cancer
Author(s) -
Chen Beibei,
Zhao Qingfang,
Guan Lulu,
Lv Huifang,
Bie Liangyu,
Huang Jinxi,
Chen XiaoBing
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13726
Subject(s) - carcinogenesis , long non coding rna , gene silencing , gene knockdown , cancer research , biology , cell cycle , cancer , e2f1 , cell growth , microbiology and biotechnology , rna , cell culture , genetics , gene
Abstract Long non‐coding RNA s (lnc RNA s) have been illustrated to function as important regulators in carcinogenesis and cancer progression. However, the roles of lnc RNA NNT ‐ AS 1 in gastric cancer remain unclear. In the present study, we investigate the biological role of NNT ‐ AS 1 in gastric cancer tumorigenesis. Results revealed that NNT ‐ AS 1 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 ‐ AS 1 indicated the poor prognosis of GC patients. In vitro experiments validated that NNT ‐ AS 1 knockdown suppressed the proliferation and invasion ability and induced the GC cell cycle progression arrest at G0/G1 phase. In vivo xenograft assay, NNT ‐ AS 1 silencing decreased the tumour growth of GC cells. Bioinformatics online program predicted that miR‐424 targeted the 3′‐ UTR of NNT ‐ AS 1. Luciferase reporter assay, RNA ‐immunoprecipitation ( RIP ) and RNA pull‐down assay validated the molecular binding within NNT ‐ AS 1 and miR‐424, therefore jointly forming the RNA ‐induced silencing complex ( RISC ). Moreover, E2F1 was verified to act as the target gene of NNT ‐ AS 1/miR‐424, indicating the NNT ‐ AS 1/miR‐424/E2F1 axis. In conclusion, our study indicates that NNT ‐ AS 1 sponges miR‐424/E2F1 to facilitate GC tumorigenesis and cycle progress, revealing the oncogenic role of NNT ‐ AS 1 for GC .