microRNA-192 suppresses leptomeningeal dissemination of medullpblastoma by modulating cell proliferation and anchoring through the regulation dihydrofolate reductase, integrin subunits, and CD 47

Abstract

Introduction: The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the role of microRNAs (miRNAs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify the miRNA involved in leptomeningeal dissemination and to elucidate its target mechanisms.

Materials and methods: We analyzed the miRNA expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. Differentially expressed miRNAs (DEmiRNAs) were validated on 29 medulloblastoma tissues and three medulloblastoma cells. The biological function of the selected miRNA was evaluated using in vitro studies.

Results: A total of 12 DEmiRNAs were identified including miRNA-192 in medulloblastoma with seeding. The reduced expression of miRNA-192 was confirmed in the tumor seeding group and in the medulloblastoma cell lines. Overexpression of miRNA-192 inhibited cellular proliferation targeting dihydrofolate reductase (DHFR). miRNA-192 decreased cellular anchoring via the repression of integrin subunits (αV, β1, and β3) and CD47.

Conclusions: Medulloblastoma with seeding showed specific DEmiRNAs compared to those without. microRNA-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring ability.