MiR-101 reverses the hypomethylation of the LMO3 promoter in glioma cells

// Xiaoping Liu 1, 2 * , Qianqian Lei 1 * , Zhibin Yu 1 , Gang Xu 1, 4 , Hailin Tang 2 , Wei Wang 1 , Zeyou Wang 1 , Guiyuan Li 3, 1 , Minghua Wu 3, 1 1 Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China 2 Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China 3 School of Basic Medical Science, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha 410078, Hunan, China 4 Medical College, University of South China, Hengyang 421001, Hunan, China * These authors have contributed equally to this work Correspondence to: Minghua Wu, e-mail: wuminghua554@aliyun.com Guiyuan Li, e-mail: lgy@csu.edu.cn Keywords: Epigenetics, MiR-101, LIM-only protein 3, Apoptosis, Polycomb Repressive Complex 2 Received: November 11, 2014      Accepted: January 23, 2015      Published: February 11, 2015 ABSTRACT LIM-only protein 3 (LMO3), a member of the LIM-only protein group, is a new DNA methylation gene that was identified in gliomas via the MeDIP-Chip in our previous study. In this study, we found that LIM-only protein 3 (LMO3) is hypomethylated and overexpressed in glioma cells and tissues. The overexpression of LMO3 was correlated with a poor prognosis in glioma patients, and LMO3 was indirectly inhibited by the tumor suppressor miR-101, which is a potential prognosis marker of gliomas. MiR-101 decreased the expression of LMO3 by reversing the methylation status of the LMO3 promoter and by inhibiting the presence of the methylation-related histones H3K4me2 and H3K27me3 and increasing the presence of H3K9me3 and H4K20me3 on the promoter. It was determined that miR-101 decreases the occupancy of H3K27me3 by inhibiting EZH2, DNMT3A and EED and decreases the H3K9me3 occupancy on the LMO3 promoter via SUV39H1, SUV39H2, G9a and PHF8. Furthermore, miR-101 suppresses the expression of LMO3 by decreasing USF and MZF1.