Oncotarget

Research Papers:

Epigenetic modification of miR-141 regulates SKA2 by an endogenous ‘sponge’ HOTAIR in glioma

Er-Bao Bian, Chun-Chun Ma, Xiao-Jun He, Chao Wang, Gang Zong, Hong-Liang Wang and Bing Zhao _

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Oncotarget. 2016; 7:30610-30625. https://doi.org/10.18632/oncotarget.8895

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Abstract

Er-Bao Bian1,2,*, Chun-Chun Ma1,2,*, Xiao-Jun He1,2,*, Chao Wang1,2, Gang Zong1,2, Hong-Liang Wang1,2, Bing Zhao1,2

1Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China

2Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China

*These author contribute equally to the first author

Correspondence to:

Bing Zhao, e-mail: [email protected]

Keywords: gliomas, miR-141, HOTAIR, SKA2, DNMT1

Received: November 16, 2015     Accepted: March 31, 2016     Published: April 21, 2016

ABSTRACT

Aberrant expression of miR-141 has recently implicated in the occurrence and development of various types of malignant tumors. However whether the involvement of miR-141 in the pathogenesis of glioma remains unknown. Here, we showed that miR-141 was markedly downregulated in glioma tissues and cell lines compared with normal brain tissues, and its expression correlated with the pathological grading. Enforced expression of miR-141 in glioma cells significantly inhibited cell proliferation, migration and invasion, whereas knockdown of miR-141 exerted opposite effect. Mechanistic investigations revealed that HOTAIR might act as an endogenous ‘sponge’ of miR-141, thereby regulating the derepression of SKA2. Further, we explored the molecular mechanism by which miR-141 expression was regulated, and found that the miR-141 promoter was hypermethylated and that promoter methylation of miR-141 was mediated by DNMT1 in glioma cells. Finally, both overexpression of miR-141 and knockdown of HOTAIR in a mouse model of human glioma resulted in significant reduction of tumor growth in vivo. Collectively, these results suggest that epigenetic modification of miR-141 and the interaction of ceRNA regulatory network will provide a new approach for therapeutics against glioma.


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