<p>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)</p>

Abstract

Background: MicroRNAs 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 Methods: We 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. Results: DE-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. Conclusion: We 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. Keywords: glioblastoma, hsa-miR-338-3p , OXSM , fatty acid metabolism

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