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