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).

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 is a direct target of . Flow cytometry was used to detect the effects of 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 " and 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 regulates fatty acid metabolism by directly targeting 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 inhibitor antagonized the effect of downregulation of on cell cycle and apoptosis of GBM cells.

CONCLUSION

We revealed that , down-regulated in GBM, may affect the biogenesis and rapid proliferation of glioma cells by regulating the level of , providing new insights into understanding the pathogenesis of GBM and developing strategies to improve GBM prognosis.