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PMID: 24775712 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer.

Molecular cancer ·Vol. 13 ·2014-04-28 ·Pages 92

Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, Kong R, Xia R, Lu KH, Li JH, De W, Wang KM, Wang ZX

Abstract

Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.

MeSH Terms
Animals Base Sequence Biomarkers, Tumor/genetics,metabolism Carcinoma/genetics,metabolism,mortality,pathology Cell Proliferation Cell Survival Female Gene Expression Regulation, Neoplastic Humans Lymphatic Metastasis Male Mice Mice, Nude MicroRNAs/genetics,metabolism Molecular Sequence Data Neoplasm Transplantation RNA, Long Noncoding/genetics,metabolism Receptor, ErbB-2/genetics,metabolism Signal Transduction Stomach Neoplasms/genetics,metabolism,mortality,pathology Survival Analysis Tumor Microenvironment
Chemicals
Biomarkers, Tumor HOTAIR long untranslated RNA, human MIRN331 microRNA, human MicroRNAs RNA, Long Noncoding ERBB2 protein, human Receptor, ErbB-2
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Liu Xiang-Hua
Sun Ming
Nie Feng-Qi
Ge Ying-Bin
Zhang Er-Bao
Yin Dan-Dan
Kong Rong
Xia Rui
Lu Kai-Hua
Li Jin-Hai
De Wei
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China. dewei@njmu.edu.cn.
Wang Ke-Ming
Wang Zhao-Xia
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Article Info
Journal
Molecular cancer
Abbr.
Mol Cancer
ISSN
1476-4598
DOI
10.1186/1476-4598-13-92
Email
dewei@njmu.edu.cn
Published
2014-04-28
Epub
2014-00-28
Pages
92
Language
English
Region
England
NLM ID
101147698
PMCID
PMC4021402
Subset
IM
External Links
PubMed source DOI: 10.1186/1476-4598-13-92 PMC Full Text View journal details
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