Reduced Expression of hsa-miR-338-3p Contributes to the Development of Glioma Cells by Targeting Mitochondrial 3-Oxoacyl-ACP Synthase (OXSM) in Glioblastoma (GBM).

Abstract

BackgroundMicroRNAs have been identified as major regulators and therapeutic targets of glioblastoma (GBM). It is thus meaningful to study the miRNAs differentially expressed (DE-miRNAs) in GBM.Materials and MethodsWe performed a meta-analysis of previously published microarray data using the R-based “metaMA” package to identify DE-miRNAs.The biological processes of the DE-miRNAs were then analyzed using FunRich. KEGG pathways of the DE-miRNAs gene targets were analyzed by mirPath V.3. Luciferase activity assay was performed to validate that OXSM is a direct target of hsa-miR338-3p. Flow cytometry was used to detect the effects of miR-338-3p on GBM cell proliferation, apoptosis and cell cycle.ResultsDE-miRNAs in blood and brain tissue from GBM were identified. “Type I interferon signaling pathway” and “VEGF and VEGFR signaling network” were the most significantly enriched biological processes shared by all GBM types. In KEGG pathway analysis, DE-miRNAs both in blood and tissue show altered fatty acid biosynthesis. Further validation shows hsa-miR-338-3p regulates fatty acid metabolism by directly targeting OXSM gene. In addition, our data revealed an accelerated cell cycle and an anti-apoptotic role for OXSM in glioma cells, which has not been reported. Finally, we confirmed that hsa-miR-338-3p inhibitor antagonized the effect of downregulation of OXSM on cell cycle and apoptosis of GBM cells.ConclusionWe revealed that hsa-miR-338-3p, down-regulated in GBM, may affect the biogenesis and rapid proliferation of glioma cells by regulating the level of OXSM, providing new insights into understanding the pathogenesis of GBM and developing strategies to improve GBM prognosis.