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

// Er-Bao Bian 1, 2, * , Chun-Chun Ma 1, 2, * , Xiao-Jun He 1, 2, * , Chao Wang 1, 2 , Gang Zong 1, 2 , Hong-Liang Wang 1, 2 , Bing Zhao 1, 2 1 Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China 2 Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China * These author contribute equally to the first author Correspondence to: Bing Zhao, e-mail: aydzhb@126.com 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.