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MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3).
Kanchan, Ranjana K; Perumal, Naveenkumar; Atri, Pranita; Chirravuri Venkata, Ramakanth; Thapa, Ishwor; Klinkebiel, David L; Donson, Andrew M; Perry, Deborah; Punsoni, Michael; Talmon, Geoffrey A; Coulter, Donald W; Boue', Daniel R; Snuderl, Matija; Nasser, Mohd W; Batra, Surinder K; Vibhakar, Rajeev; Mahapatra, Sidharth.
Afiliação
  • Kanchan RK; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
  • Perumal N; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
  • Atri P; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
  • Chirravuri Venkata R; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
  • Thapa I; School of Interdisciplinary Informatics, University of Nebraska at Omaha, Omaha, NE.
  • Klinkebiel DL; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
  • Donson AM; Morgan Adams Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Denver, CO.
  • Perry D; Department of Pathology, Children's Hospital and Medical Center, Omaha, NE.
  • Punsoni M; Department of Pathology, University of Nebraska Medical Center, Omaha, NE.
  • Talmon GA; Department of Pathology, University of Nebraska Medical Center, Omaha, NE.
  • Coulter DW; Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE.
  • Boue' DR; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital and the Ohio State University, Columbus, OH.
  • Snuderl M; Department of Pathology, New York University Langone Health, New York, NY.
  • Nasser MW; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
  • Batra SK; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
  • Vibhakar R; Morgan Adams Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Denver, CO.
  • Mahapatra S; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE.
Brain Pathol ; 30(4): 732-745, 2020 07.
Article em En | MEDLINE | ID: mdl-32145124
ABSTRACT
Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR-1253, a brain-enriched microRNA that regulates bone morphogenic proteins during cerebellar development. We hypothesized miR-1253 confers novel tumor-suppressive properties in medulloblastoma. Using two different cohorts of medulloblastoma samples, we first studied the expression and methylation profiles of miR-1253. We then explored the anti-tumorigenic properties of miR-1253, in parallel with a biochemical analysis of apoptosis and proliferation, and isolated oncogenic targets using high-throughput screening. Deregulation of miR-1253 expression was noted, both in medulloblastoma clinical samples and cell lines, by epigenetic silencing via hypermethylation; specific de-methylation of miR-1253 not only resulted in rapid recovery of expression but also a sharp decline in tumor cell proliferation and target gene expression. Expression restoration also led to a reduction in tumor cell virulence, concomitant with activation of apoptotic pathways, cell cycle arrest and reduction of markers of proliferation. We identified two oncogenic targets of miR-1253, CDK6 and CD276, whose silencing replicated the negative trophic effects of miR-1253. These data reveal novel tumor-suppressive properties for miR-1253, i.e., (i) loss of expression via epigenetic silencing; (ii) negative trophic effects on tumor aggressiveness; and (iii) downregulation of oncogenic targets.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação Neoplásica da Expressão Gênica / Neoplasias Cerebelares / MicroRNAs / Quinase 6 Dependente de Ciclina / Antígenos B7 / Meduloblastoma Limite: Humans Idioma: En Revista: Brain Pathol Assunto da revista: CEREBRO / PATOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Níger

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação Neoplásica da Expressão Gênica / Neoplasias Cerebelares / MicroRNAs / Quinase 6 Dependente de Ciclina / Antígenos B7 / Meduloblastoma Limite: Humans Idioma: En Revista: Brain Pathol Assunto da revista: CEREBRO / PATOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Níger