title: Disturbing miR-182 and -381 inhibits BRD7 transcription and glioma growth by directly targeting LRRC4.
abstract: Inactivated LRRC4 has been clinically detected in gliomas, and promoter hypermethylation has been implicated as the mechanism of inactivation in some of those tumors. Our previous researches indicated that LRRC4 is a target gene of miR-381, the interaction of miR-381 and LRRC4 is involved in glioma growth. In this study, we demonstrate that LRRC4 is a target gene of the other microRNA, miR-182. We found that the high expression of miR-182 and miR-381 in gliomas are involved in pathological malignant progression. The silencing of miR-182 and miR-381 inhibited the proliferation in vitro and growth of glioma cell with in vivo magnetic resonance imaging by intracranial transplanted tumor model in rats. We also demonstrated that BRD7, a transcriptional cofactor for p53, is highly expressed and negatively correlated with LRRC4 expression in gliomas. Disturbing miR-182 and miR-381 affected transcriptional regulation of the BRD7 gene. This finding was verified by ectopic overexpression of LRRC4 or restoration of endogenous LRRC4 expression by treatment with the DNA demethylating agent 5-Aza-dC. Taken together, miR-182 and miR-381 may be a useful therapeutic target for treatment of glioma.
authors.affiliation: Cancer Research Institute, Central South University,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China ; Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Cancer Research Institute, Central South University,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: Zeyou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The Center for Skull Base Surgery and Neurooncology, Hunan Province, Changsha, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Central South University,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China ; Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Central South University,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China ; The Center for Skull Base Surgery and Neurooncology, Hunan Province, Changsha, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.affiliation: Cancer Research Institute, Central South University,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic; D047368:Tumor Burden; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C503331:LRRC4 protein, human; C588249:MIRN381 microRNA, human; C538984:Mirn182 microRNA, human