title: MiR-101 reverses the hypomethylation of the LMO3 promoter in glioma cells.
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.
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.|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.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.|Medical College, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.
authors.forename: Zeyou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 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.|Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: 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.|Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006657:Histones; D060588:LIM Domain Proteins; C502335:LMO3 protein, human; C534072:MIRN101 microRNA, human; D035683:MicroRNAs
keywords: LIM-only protein 3; apoptosis; epigenetics; miR-101; polycomb repressive complex 2
references.citation: Cancer Biol Ther. 2014 Sep;15(9):1248-55
references.pmid: 24971953
references.citation: Biochem Biophys Res Commun. 2012 Aug 24;425(2):462-7
references.pmid: 22846578
references.citation: Brain Res. 2011 May 19;1391:125-31
references.pmid: 21439273
references.citation: Cell Physiol Biochem. 2014;34(2):413-22
references.pmid: 25059472
references.citation: Mol Cell Biochem. 2014 Sep;394(1-2):23-30
references.pmid: 24833465
references.citation: ScientificWorldJournal. 2014;2014:794756
references.pmid: 25013866
references.citation: Biochem Biophys Res Commun. 2014 Apr 18;446(4):1053-9
references.pmid: 24661879
references.citation: Genes Dev. 2013 Jan 15;27(2):197-210
references.pmid: 23322301
references.citation: Brain Res. 2009 Apr 10;1265:24-9
references.pmid: 19236851
references.citation: Neuro Oncol. 2014 Jul;16(7):896-913
references.pmid: 24842956
references.citation: Anal Biochem. 2010 Feb 1;397(1):96-106
references.pmid: 19835834
references.citation: Mol Cancer. 2011 Sep 30;10:124
references.pmid: 21962230
references.citation: Cell Rep. 2014 Aug 7;8(3):743-53
references.pmid: 25066127
references.citation: PLoS One. 2011 May 05;6(5):e19297
references.pmid: 21573214
references.citation: Cancer Res Treat. 2014 Jul;46(3):209-22
references.pmid: 25038756
references.citation: Nucleic Acids Res. 2014 Oct 29;42(19):12041-51
references.pmid: 25260594
references.citation: Biochem Biophys Res Commun. 2014 Aug 15;451(1):119-25
references.pmid: 25065740
references.citation: Aging (Albany NY). 2014 Jul;6(7):545-63
references.pmid: 25063769
references.citation: Nature. 2014 Oct 9;514(7521):247-51
references.pmid: 25119042
references.citation: Protein Cell. 2014 Nov;5(11):837-50
references.pmid: 24952722
references.citation: Surgery. 2012 Oct;152(4):704-11; discussion 711-3
references.pmid: 22943841
references.citation: Nat Neurosci. 2013 Dec;16(12):1745-53
references.pmid: 24162653
references.citation: Oncol Lett. 2014 Feb;7(2):461-465
references.pmid: 24396470
references.citation: J Biomed Sci. 2010 May 06;17:35
references.pmid: 20444294
references.citation: Development. 2012 Dec;139(24):4633-43
references.pmid: 23136391
references.citation: In Vitro Cell Dev Biol Anim. 2001 Nov-Dec;37(10):684-90
references.pmid: 11776974
references.citation: J Neurooncol. 2012 May;107(3):479-85
references.pmid: 22160665
references.citation: Cell Death Dis. 2013 Jun 20;4:e675
references.pmid: 23788032
references.citation: Int J Gynecol Cancer. 2014 Sep;24(7):1165-72
references.pmid: 24987920
references.citation: PLoS One. 2014 Sep 08;9(9):e106962
references.pmid: 25198515
references.citation: Brain Tumor Res Treat. 2014 Apr;2(1):7-21
references.pmid: 24926467
references.citation: J Thorac Oncol. 2012 Jan;7(1):20-33
references.pmid: 22011669
references.citation: Cancer Cell. 2013 Nov 11;24(5):660-72
references.pmid: 24183680
references.citation: Cancer Res. 2005 Jun 1;65(11):4587-97
references.pmid: 15930276
references.citation: Biochem Biophys Res Commun. 2010 Feb 12;392(3):252-7
references.pmid: 19995558
references.citation: Cell Death Dis. 2014 Sep 11;5:e1413
references.pmid: 25210796
references.citation: Biomed Res Int. 2013;2013:868131
references.pmid: 23509792
references.citation: Oncogene. 2015 Mar 26;34(13):1641-9
references.pmid: 24793789
references.citation: PLoS One. 2013;8(3):e58319
references.pmid: 23505487
references.citation: Biol Chem. 2003 Oct-Nov;384(10-11):1421-7
references.pmid: 14669984
references.citation: Oncotarget. 2014 Aug 15;5(15):6049-62
references.pmid: 25153722
references.citation: Oncol Lett. 2014 Oct;8(4):1815-1821
references.pmid: 25202416
references.citation: J Neurosci. 1997 Jul 15;17(14):5549-59
references.pmid: 9204936