Research Papers:
Epigenetic modification of miR-141 regulates SKA2 by an endogenous ‘sponge’ HOTAIR in glioma
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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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PII: 8895