Abstract

Background Medulloblastoma (MB), the predominant pediatric malignant brain tumor, remains poorly characterized in terms of its molecular drivers. The lack of reliable early diagnostic biomarkers and effective therapeutic targets continues to pose significant clinical challenges. Recent studies have implicated circular RNAs (circRNAs) as key regulators of diverse oncogenic pathways across multiple solid malignancies. However, the precise processes that underlie circRNAs’ function in Sonic Hedgehog (SHH)-driven MB remain unclear. Methods RNA-sequencing of three SHH-MB tumors paired with adjacent non-malignant cerebellum was first employed to profile circRNA landscapes, after which hsa_circ_PCNT abundance was precisely quantified by quantitative real-time PCR in an extended cohort of clinical specimens and in established cell lines. The oncogenic and metastatic consequences of altering this transcript were subsequently interrogated through a comprehensive battery of in vitro functional assays and orthotopic xenograft models. To decipher the mechanism, we integrated dual-luciferase reporters, fluorescence in situ hybridization, RNA immunoprecipitation and biotinylated RNA pull-down, thereby demonstrating that hsa_circ_PCNT serves as a cytoplasmic sponge for hsa-miR-133b and consequently alleviates the micRNA-imposed repression of the downstream effector TAGLN2. Results Our investigations identified hsa_circ_PCNT as a significantly upregulated circRNA in SHH-MB, with its circular conformation being experimentally validated. Genetic knockdown of this circRNA exerted profound tumor-suppressive effects, including enhanced apoptosis coupled with impaired proliferative capacity, migratory potential, and invasive behavior in vitro. These anti-tumorigenic properties were further corroborated in vivo through xenograft models, where hsa_circ_PCNT depletion markedly attenuated tumor formation. Mechanistically, we established that hsa_circ_PCNT operates as a competitive endogenous