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PMID: 24810364 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a.

Oncotarget ·Vol. 5 ·No. 8 ·2014-04-30 ·Pages 2276-92

Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, Xu TP, Xia R, Yang JS, De W, Chen Jf

Abstract

Long noncoding RNAs are involved in diseases including cancer. 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 a higher TNM stage (P=0.041) and tumor size (P=0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (P=0.036). Further experiments revealed that ANRIL knockdown significantly repressed the proliferation both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is in part 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 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 candidate prognostic biomarker and target for new therapies in human gastric cancer.

MeSH Terms
Animals Blotting, Western Chromatin Immunoprecipitation Disease-Free Survival Epigenesis, Genetic Female Flow Cytometry Gene Expression Regulation, Neoplastic/genetics Gene Silencing Heterografts Humans Immunohistochemistry Kaplan-Meier Estimate Male Mice Mice, Inbred BALB C MicroRNAs/genetics Middle Aged Prognosis Proportional Hazards Models RNA, Long Noncoding/genetics Real-Time Polymerase Chain Reaction Stomach Neoplasms/genetics,mortality Transfection
Chemicals
CDKN2B antisense RNA, human MIRN449 microRNA, human MIRN99 microRNA, human MicroRNAs RNA, Long Noncoding
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Zhang Er-bao
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Kong Rong
Yin Dan-dan
You Liang-hui
Sun Ming
Han Liang
Xu Tong-peng
Xia Rui
Yang Jin-song
De Wei
Chen Jin fei
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Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.1902
Published
2014-04-30
Pages
2276-92
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC4039162
Subset
IM
External Links
PubMed source DOI: 10.18632/oncotarget.1902 PMC Full Text View journal details
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