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Genetic alterations in microRNAs in medulloblastomas

Genetic alterations in microRNAs in medulloblastomas

Authors :
Sheng-Qing, Lv
Young-Ho, Kim
Fiaschetti, Giulio
Tarek, Shalaby
Sumihito, Nobusawa
Hui, Yang
Zheng, Zhou
Michael, Grotzer
Hiroko, Ohgaki
Source :
Brain Pathol
Publication Year :
2011

Abstract

MicroRNAs (miRNAs) regulate a variety of cellular processes via the regulation of multiple target genes. We screened 48 medulloblastomas for mutation, deletion and amplification of nine miRNA genes that were selected on the basis of the presence of potential target sequences within the 3′‐untranslated region of the MYCC mRNA. Differential PCR revealed deletions in miR‐186 (15%), miR‐135a‐1 (33%), miR‐548d‐1 (42%), miR‐548d‐2 (21%) and miR‐512‐2 (33%) genes, whereas deletion or amplification was detected in miR‐135b (23%) and miR‐135a‐2 (15%). In miR‐33b, deletion, amplification or a mutation at the precursor miRNA were detected in 10% of medulloblastomas. Overall, 35/48 (73%) medulloblastomas had at least one alteration. Real‐time RT‐PCR revealed MYCC overexpression in 11 of 37 (30%) medulloblastomas, and there was a correlation between MYCC overexpression and miR‐512‐2 gene deletion (P = 0.0084). Antisense‐based knockdown of miR‐512‐5p (mature sequence of miR‐512‐2) resulted in significant upregulation of MYCC expression in HeLa and A549 cells, while forced overexpression of miR‐512‐2 in medulloblastoma/PNET cell lines DAOY, UW‐228‐2, PFSK resulted in the downregulation of MYCC protein. Furthermore, the results of luciferase reporter assays suggested that miR‐512‐2 targets the MYCC gene. These results suggest that alterations in the miRNA genes may be an alternative mechanism leading to MYCC overexpression in medulloblastomas.

Details

ISSN :
17503639
Volume :
22
Issue :
2
Database :
OpenAIRE
Journal :
Brain pathology (Zurich, Switzerland)
Accession number :
edsair.pmid..........e451b59297e9ce91378d5a72035d5a44