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Genetic alterations in microRNAs in medulloblastomas
Genetic alterations in microRNAs in medulloblastomas
- 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.
- Subjects :
- Adult
Male
Lung Neoplasms
Adolescent
Gene Amplification
Infant
Middle Aged
Gene Expression Regulation, Neoplastic
Proto-Oncogene Proteins c-myc
MicroRNAs
Young Adult
HEK293 Cells
Child, Preschool
Mutation
Humans
Female
Genetic Predisposition to Disease
Genetic Testing
Cerebellar Neoplasms
Child
Gene Deletion
Research Articles
HeLa Cells
Medulloblastoma
Subjects
Details
- ISSN :
- 17503639
- Volume :
- 22
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Brain pathology (Zurich, Switzerland)
- Accession number :
- edsair.pmid..........e451b59297e9ce91378d5a72035d5a44