title: MicroRNA-31 suppresses medulloblastoma cell growth by inhibiting DNA replication through minichromosome maintenance 2.
abstract: Medulloblastoma is an aggressive childhood brain tumor with poor prognosis. Recent studies indicate that dys-regulation of microRNA expression plays important roles in tumorigenesis. By comparing microRNA levels between mouse medulloblastoma and normal cerebellar tissues, we identified a set of down-regulated microRNAs including miR-31. Here, we show that the genomic region surrounding human miR-31 at 9p21.3 is frequently deleted in many solid tumor cell lines, and reintroducing miR-31 into DAOY cells, a line of human medulloblastoma cells devoid of miR-31, strongly suppresses cell growth, causes cell cycle arrest at the G1/S boundary, and inhibits colony formation in vitro and xenograft tumorigenesis in nude mice. Global gene expression profiling of mouse medulloblastomas and bioinformatics analyses of microRNA targets suggest that minichromosome maintenance complex component 2 (MCM2) is a likely target gene of miR-31 in suppressing cell growth. We demonstrate that miR-31 inhibits MCM2 expression via its 3'-untranslated region, that knockdown of MCM2 in DAOY cells leads to a degree of growth inhibition comparable to that by miR-31 restoration, and that overexpression of miR-31 reduces the chromatin loading of MCM2 at the point of G1/S transition. Taken together, these data indicate that miR-31 suppresses medulloblastoma tumorigenesis by negatively regulating DNA replication via MCM2.
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China. These authors contributed equally to this work.
authors: Yucui
authors: Y
authors: Jin
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China. Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China. These authors contributed equally to this work.
authors: Anwen
authors: A
authors: Xiong
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Ziyu
authors: Z
authors: Zhang
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Sanen
authors: S
authors: Li
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Huijie
authors: H
authors: Huang
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Ting-ting
authors: TT
authors: Yu
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xiumei
authors: X
authors: Cao
authors: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Steven Y
authors: SY
authors: Cheng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004261:DNA Replication / Q000235:genetics*; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D061986:MCF-7 Cells; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D064111:Minichromosome Maintenance Complex Component 2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2