Regulation of HOXA11-AS/miR-214-3p/EZH2 axis on the growth, migration and invasion of glioma cells

Glioma is one of the most common and aggressive malignant tumors in central nervous system. Recently, long non-coding RNA (lncRNA) HOXA11-AS has been reported to be an oncogenic gene in multiple cancers. However, the molecular mechanisms of HOXA11-AS involved in cancer progression of human glioma re...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2017-11, Vol.95, p.1504-1513
Main Authors: Xu, Chenyang, He, Tao, Li, Zhenjiang, Liu, Honglin, Ding, Bingqian
Format: Article
Language:English
Subjects:
Base Sequence
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Enhancer of Zeste Homolog 2 Protein - metabolism
EZH2
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Glioma
Glioma - genetics
Glioma - pathology
HOXA11-AS
Humans
lncRNA
Male
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
miR-214-3p
Neoplasm Invasiveness
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
RNA, Small Interfering - metabolism
Up-Regulation - genetics
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Summary:Glioma is one of the most common and aggressive malignant tumors in central nervous system. Recently, long non-coding RNA (lncRNA) HOXA11-AS has been reported to be an oncogenic gene in multiple cancers. However, the molecular mechanisms of HOXA11-AS involved in cancer progression of human glioma remain unknown. The expression levels of HOXA11-AS in 45 paired primary glioma tissues and cell lines were examined by quantitative real-time PCR, and the correlation between HOXA11-AS expression and clinicopathologic characteristics of patients with glioma were analyzed. HOXA11-AS was knockdown in glioma cells by transfection with HOXA11-AS siRNA, and cell proliferation, migration and invasion were detected. The tumor growth of xenografts with HOXA11-AS knockdown glioma cells was also analyzed. The expression levels of HOXA11-AS were significantly up-regulated in glioma tissues and cell lines compared with that in adjacent normal brain tissues and normal human astrocytes (NHA). High expression of HOXA11-AS was correlated with shorter overall survival in patients with glioma. Knockdown of HOXA11-AS inhibited glioma cell proliferation, migration and invasion in vitro, and tumor growth in vivo. In addition, we demonstrated that HOXA11-AS functioned as a competing endogenous RNA (ceRNA) for miR-214-3p, which in turn positively regulated the expression of its direct target EZH2. We demonstrated that HOXA11-AS acted as an oncogenic lncRNA that promoted cell growth and metastasis of glioma through regulating miR-214-3p/EZH2 axis. These results suggested HOXA11-AS may serve as an efficient marker and a potential therapeutic target for glioma.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2017.08.097