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Updated: Jun 18, 2025
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Identification and validation of miRNA-target genes network in pediatric brain tumors
Renata Gruszka1, Jakub Zakrzewski2, Emilia Nowosławska3
1Faculty of Biology and Environmental Protection, Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland. renata.gruszka@biol.uni.lodz.pl.
Abstract:
Alterations in miRNA levels have been observed in various types of cancer, impacting numerous cellular processes and increasing their potential usefulness in combination therapies also in brain tumors. Recent advances in understanding the genetics and epigenetics of brain tumours point to new aberrations and associations, making it essential to continually update knowledge and classification. Here we conducted molecular analysis of 123 samples of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma), focusing on identification of genes that could potentially be regulated by crucial representatives of OncomiR-1: miR-17-5p and miR-20a-5p. On the basis of microarray gene expression analysis and qRTPCR profiling, we selected six (WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11) the most promising target genes for further experiments. The WEE1, CCND1, PTPRO, TP53INP1 genes showed increased expression levels in all tested entities with the lowest increase in the pilocytic astrocytoma compared to the ependymoma and medulloblastoma. The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research.
Insights
MicroRNA alterations in childhood brain tumors reveal potential therapeutic targets. Gene expression analysis identified key genes regulated by OncomiR-1, correlating with tumor grade and subtype.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) alterations are implicated in cancer, affecting cellular processes and offering potential for combination therapies, including in brain tumors.
- Advances in brain tumor genetics and epigenetics necessitate continuous knowledge updates and classification refinement.
Purpose of the Study:
- To conduct molecular analysis of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma).
- To identify genes potentially regulated by OncomiR-1 members (miR-17-5p and miR-20a-5p).
Main Methods:
- Microarray gene expression analysis and quantitative reverse transcription PCR (qRTPCR) profiling.
- Analysis of 123 childhood brain tumor samples.
- Selection of six candidate target genes: WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11.
Main Results:
- WEE1, CCND1, PTPRO, and TP53INP1 genes exhibited increased expression across all tested tumor types.
- Pilocytic astrocytoma showed a lower increase in these genes compared to ependymoma and medulloblastoma.
- Gene expression levels correlated with World Health Organization (WHO) grade and tumor subtype.
Conclusions:
- The findings suggest that integrated genomic and epigenetic pathway analysis is crucial for future molecular research in brain tumors.
- Identified gene expression patterns offer insights into potential therapeutic strategies and molecular classification of childhood brain tumors.
