Impact of dcEF on microRNA profiles in glioblastoma and exosomes using a novel microfluidic bioreactor

Abstract

Glioblastoma multiforme, the most common type of highly aggressive primary brain tumor, is influenced by complex molecular signaling pathways, where microRNAs (miRNAs) play a critical regulatory role. Originating from glial cells, glioblastoma cells are affected by the physiological direct current electric field (dcEF) in the central nervous system. While dcEF has been shown to affect glioblastoma migration (electrotaxis), the specific impact on glioblastoma intercellular communication and miRNA expression in glioblastoma cells and their exosomes remains unclear. This study aims to fill this gap by investigating the differential expression of microRNAs in glioblastoma cells and exosomes under dcEF stimulation. We have developed a novel, reversibly sealed dcEF stimulation bioreactor that ensures uniform dcEF stimulation across a large cell culture area, specifically targeting glioblastoma cells and primary human astrocytes. Using microarray analysis, we examined differential miRNA profiles in both cellular and exosomal RNAs. Our study identified shared molecular targets and pathways affected by dcEF stimulation. Our findings reveal significant changes in miRNA expression due to dcEF stimulation, with specific miRNAs, such as hsa-miR-4440 being up-regulated and hsa-miR-3201 and hsa-mir-548g being down-regulated. Future research will focus on elucidating the molecular mechanisms of these miRNAs and their potential as diagnostic biomarkers. The developed platform offers high-quality dcEF stimulation and rapid sample recovery, with potential applications in tissue engineering and multi-omics molecular analysis.