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PMID: 26136075 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

LincHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer.

Cell death & disease ·Vol. 6 ·2015-07-02 ·Pages e1802

Liu YW, Sun M, Xia R, Zhang EB, Liu XH, Zhang ZH, Xu TP, De W, Liu BR, Wang ZX

Abstract

lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.

MeSH Terms
Animals Antigens, CD Biomarkers, Tumor/genetics Cadherins/biosynthesis Cell Line, Tumor Cell Movement/genetics Down-Regulation/genetics Enhancer of Zeste Homolog 2 Protein Epithelial-Mesenchymal Transition/genetics Gene Expression Regulation, Neoplastic Gene Silencing Histones/genetics Humans Male Mice Mice, Nude MicroRNAs/genetics Neoplasm Invasiveness/genetics Neoplasm Metastasis/genetics Neoplasm Proteins Polycomb Repressive Complex 2/genetics Promoter Regions, Genetic/genetics RNA Interference RNA, Long Noncoding/genetics RNA, Small Interfering Snail Family Transcription Factors Stomach Neoplasms/genetics,pathology Transcription Factors/biosynthesis,metabolism
Chemicals
Antigens, CD Biomarkers, Tumor CDH1 protein, human Cadherins HOTAIR long untranslated RNA, human Histones MIRN34 microRNA, human MicroRNAs Neoplasm Proteins RNA, Long Noncoding RNA, Small Interfering SUZ12 protein, human Snail Family Transcription Factors Transcription Factors EZH2 protein, human Enhancer of Zeste Homolog 2 Protein Polycomb Repressive Complex 2
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Liu Y-w
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Sun M
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Xia R
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Zhang E-b
Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
Liu X-h
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Zhang Z-h
Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
Xu T-p
Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
De W
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Liu B-r
Department of Oncology, Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, PR China.
Wang Z-x
Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
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Article Info
Journal
Cell death & disease
Abbr.
Cell Death Dis
ISSN
2041-4889
DOI
10.1038/cddis.2015.150
Published
2015-07-02
Epub
2015-00-02
Pages
e1802
Language
English
Region
England
NLM ID
101524092
PMCID
PMC4650715
Subset
IM
External Links
PubMed source DOI: 10.1038/cddis.2015.150 PMC Full Text View journal details
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