MEDB-02. The identification and functional characterization of circular RNA Circ_63706 in sonic hedgehog medulloblastomas

Circular RNAs (circRNAs) are increasingly recognized as stable and specific biomarkers and therapeutic targets in many cancers, but little is known about their function, subtype specificity, and biomarker potential in medulloblastomas. Medulloblastoma is a central nervous system tumor that predominantly affects children and always requires aggressive therapy. Understanding and identifying novel disease-related molecular mechanisms and pathways are essential for developing optimal and novel therapies. To identify medulloblastoma subgroup-specific circRNAs, we subjected RNA-seq data from 175 clinical medulloblastoma samples representing the four subgroups to a statistical and machine learning (random forest classification) pipeline. Circular RNA circ_63706 expression was specific to the sonic hedgehog (SSH) group, which was confirmed through in situ hybridization analysis of clinical tissue samples. Functional characterization of circ_63706 by siRNAs and shRNAs demonstrated that cell proliferation, invasion, and apoptosis are perturbed in circ_63706 cells and inhibited in vivo tumor growth. These novel medulloblastoma-specific circular RNAs are emerging as important oncogenes that not only provide valuable mechanistic insights into how medulloblastomas develop but also how they can be used as biomarkers and therapeutic targets. These results pave the way for the specific identification and personalized treatment of different medulloblastoma subgroups.