New microRNA-based therapies reveal common targets in paediatric medulloblastoma and adult glioblastoma

The research hypothesised that miR-206 and miR-383 act as tumour suppressors in medulloblastoma (MB) and that their downregulation contributes to the aggressiveness of MB and glioblastoma (GB). By identifying and targeting the genes regulated by these microRNAs (CORO1C and SV2B), new therapeutic app...

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Hauptverfasser: Mustafov, Denis, Siddiqui, Shoib Sarwar, Lambrou, George I., Braoudaki, Maria
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Sprache:eng
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Zusammenfassung:The research hypothesised that miR-206 and miR-383 act as tumour suppressors in medulloblastoma (MB) and that their downregulation contributes to the aggressiveness of MB and glioblastoma (GB). By identifying and targeting the genes regulated by these microRNAs (CORO1C and SV2B), new therapeutic approaches could be developed for treating these aggressive brain tumours. The study employed high-throughput small-RNA sequencing to analyse the expression profiles of microRNAs in MB samples. Bioinformatics tools were used to predict the target genes of the significantly downregulated miRNAs. The expression levels of the identified targets, CORO1C and SV2B, were validated through various molecular biology techniques, including Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR), western blotting, and immunohistochemistry. Functional assays were also performed to validate the regulatory effect of miR-206 and miR-383 on their target genes. Both miR-206 and miR-383 were found to be significantly downregulated in MB samples, suggesting their potential role as tumour suppressors. Bioinformatics analysis identified CORO1C and SV2B as the target genes of miR-206 and miR-383, respectively. RT-qPCR, western blotting, and immunohistochemistry confirmed the overexpression of CORO1C/CORO1C and SV2B/SV2B in MB and GB cells and tissue samples. Functional assays validated that miR-206 and miR-383 directly regulate the expression of CORO1C and SV2B, respectively. The data suggested that the miR-206/CORO1C and miR-383/SV2B axes play a crucial role in the pathogenesis of MB and GB. The downregulation of these miRNAs leads to the overexpression of their target genes, contributing to the aggressiveness of these tumours. These findings indicate that restoring the levels of miR-206 and miR-383, or directly targeting CORO1C and SV2B, could be a promising therapeutic strategy for treating aggressive brain malignancies in both paediatric and adult patients. The identification of miR-206 and miR-383 as tumour suppressors and their target genes as therapeutic targets provides a foundation for the development of novel treatments for MB and GB. Researchers and clinicians can use this data to: o Develop miRNA mimics or gene therapy approaches to restore the levels of miR-206 and miR-383 in tumour cells. o Design small molecule inhibitors or antibodies to specifically target CORO1C and SV2B proteins. o Explore combination therapies that incorporate these new targets to impro
DOI:10.17632/yrryf4btst