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miR-512-3p as a Potential Biomarker of Poor Outcome in Pediatric Medulloblastoma
Carolina Alves Pereira Corrêa1, Pablo Shimaoka Chagas1, Mirella Baroni1
1Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Abstract:
The tumorigenesis of medulloblastoma (MB), the most frequent malignant brain tumor in children, is not completely known. MicroRNA (miRNA) expression profiles have been associated with human cancers; however, the role played by miRNAs in pediatric MB has been poorly explored. Global miRNA expression in MB and non-neoplastic cerebellum samples was evaluated by microarray assay. Nine miRNAs (miR-31-5p, -329, -383, -433, -485-3p, -485-5p, -491, -512-3p, and 539-5p) in 51 pediatric MB and 7 pediatric non-neoplastic cerebellum samples were chosen for validation by qRT-PCR. The validated miRNAs were less expressed in the MB samples than in the non-neoplastic controls. In our cohort of patients, higher miR-512-3p expression was associated with incomplete degree of resection, classification as high risk, classification as group 4, and poor overall survival. In silico analysis in an independent cohort of MB patients identified that some of the miR-512-3p target genes were also correlated with prognostic features. Our results have shown that miR-512-3p could be associated with poor clinical outcomes in pediatric MB, suggesting that miR-512-3p is a potential biomarker of prognosis.
Insights
Pediatric medulloblastoma (MB) has poorly understood tumorigenesis. This study identifies miR-512-3p as a potential prognostic biomarker, showing its lower expression in MB and association with poor outcomes in children.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Medulloblastoma (MB) is the most common malignant brain tumor in children, with incompletely understood tumorigenesis.
- MicroRNA (miRNA) expression is linked to various cancers, but their role in pediatric MB remains underexplored.
Purpose of the Study:
- To investigate global miRNA expression profiles in pediatric medulloblastoma.
- To identify specific miRNAs associated with MB tumorigenesis and clinical outcomes.
Main Methods:
- Global miRNA expression profiling using microarray assay in MB and non-neoplastic cerebellum samples.
- Validation of nine selected miRNAs (including miR-512-3p) by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 51 MB and 7 control samples.
- In silico analysis of miR-512-3p target genes in an independent MB patient cohort.
Main Results:
- Nine miRNAs, including miR-512-3p, showed lower expression in pediatric MB samples compared to non-neoplastic controls.
- Higher miR-512-3p expression correlated with incomplete resection, high-risk classification, group 4 MB, and poorer overall survival in the patient cohort.
- In silico analysis revealed that miR-512-3p target genes were associated with prognostic features in MB.
Conclusions:
- miR-512-3p expression is significantly altered in pediatric medulloblastoma.
- miR-512-3p is associated with aggressive clinical features and poor prognosis in pediatric MB patients.
- miR-512-3p represents a potential prognostic biomarker for pediatric medulloblastoma.
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