miR-324-5p acts as an independent prognostic biomarker and inhibits pediatric medulloblastoma progression by targeting HOXA9.

Abstract

Pediatric medulloblastoma (MB) represents an aggressive central nervous system malignancy in children, frequently associated with a dismal clinical prognosis. Uncovering novel epigenetic modulators is therefore paramount to advancing targeted therapeutic strategies. This study aimed to elucidate clinical relevance and dissect the post-transcriptional regulatory network of miR-324-5p in pediatric MB. miR-324-5p and HOXA9 levels were evaluated in 113 pediatric MB samples and cell lines via qRT-PCR. Prognostic significance was assessed using Kaplan-Meier and multivariate Cox regression analysis. Phenotypic alterations were explored through CCK-8 and Transwell rescue assays following oligonucleotide transfection. Luciferase reporters validated direct binding. miR-324-5p was markedly reduced in MB tissues and lines, displaying tight correlation with 17p deletion and aggressive molecular subtypes. Survival models identified diminished miR-324-5p expression as an independent predictor of adverse overall survival. In vitro, ectopic miR-324-5p expression markedly attenuated MB cell proliferation, migration, and invasion. miR-324-5p was shown to directly bind to HOXA9. HOXA9 was upregulated in MB tissues and inversely correlated with miR-324-5p. Forced HOXA9 expression partially counteracted the phenotype suppression elicited by miR-324-5p mimic in vitro. Our findings suggest that miR-324-5p functions as a critical tumor suppressor in pediatric medulloblastoma in vitro by post-transcriptionally silencing HOXA9. This axis represents a promising prognostic indicator and therapeutic target.