Mustafov Denis, Thomas Laura, Siddiqui Shoib S, Lambrou George I, Braoudaki Maria
School of Health, Medicine and Life Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK.
College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK.
Sci Rep. 2025 Jul 2;15(1):23044. doi: 10.1038/s41598-025-05517-9.
Medulloblastoma (MB), the most prevalent brain malignancy in children, presents significant challenges in paediatric oncology due to its aggressiveness and potential for relapse. Tailored treatments are crucial to mitigate treatment-related toxicities and long-term side effects on developing brains. Our study aimed to identify therapeutic targets for paediatric MB and explore common miRNA biosignatures with glioblastoma (GB), the most aggressive adult brain tumour. High-throughput small-RNA sequencing identified miR-206 and miR-383 as highly downregulated in MB samples, suggesting their tumour suppressor properties. Bioinformatics analysis identified CORO1C and SV2B as their targets. RT-qPCR, western blotting, and immunohistochemistry confirmed their overexpression in MB and GB. Elevated CORO1C expression was also found in adult MB and GB tissue samples. The role of both miRNAs on their target genes was validated through in vitro functional assays. Our study uncovers the potential role of miR-206/CORO1C and miR-383/SV2B axes as innovative therapeutic targets for combating aggressive paediatric and adult brain malignancies.
髓母细胞瘤（MB）是儿童中最常见的脑恶性肿瘤，因其侵袭性和复发可能性，给儿科肿瘤学带来了重大挑战。量身定制的治疗对于减轻与治疗相关的毒性以及对发育中大脑的长期副作用至关重要。我们的研究旨在确定小儿MB的治疗靶点，并探索与胶质母细胞瘤（GB）（最具侵袭性的成人大脑肿瘤）共有的微小RNA生物标志物。高通量小RNA测序确定miR-206和miR-383在MB样本中高度下调，表明它们具有肿瘤抑制特性。生物信息学分析确定CORO1C和SV2B为它们的靶点。逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法和免疫组织化学证实它们在MB和GB中过表达。在成人MB和GB组织样本中也发现CORO1C表达升高。通过体外功能试验验证了这两种微小RNA对其靶基因的作用。我们的研究揭示了miR-206/CORO1C和miR-383/SV2B轴作为对抗侵袭性小儿和成人大脑恶性肿瘤的创新治疗靶点的潜在作用。
