LAUSR

Glioblastoma (GBM) is the most common primary malignant intracranial adult brain tumor. Allelic deletion on chromosome 14q play an essential role in GBM pathogenesis, and this chromosome 14q site was thought to harbor multiple tumor suppressor gene associated with GBM, a region that also encodes microRNA-203 (miR-203). This study was conducted to identify gene expression profile changes associated with mir-203 expression by high-throughput RNA sequencing. Enrichment analyses for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that mir-203 expression had a strong, negative effect on a number of fundamental and interconnected biological processes involved in cell growth and proliferation. The biological processes mostly influenced were p53 signaling pathway, FoxO signaling pathway, DNA replication, cell cycle, MAPK signaling pathway and Apoptosis. In total, 847 upregulated and 345 downregulated differentially expressed genes (DEGs) were identified in control versus miR203 expressing glioma cells. After GO enrichment, the downregulated DEGs and miR-203 predicted target genes such as BCL-2, SPARC, PDGFA, CREB were found to be mainly enriched in cell cycle regulation and apoptosis processes, whereas the upregulated DEGs, such as CCND1, E2F1 were involved in the DNA replication and cell cycle regulation of gene expression. We also demonstrate that mir-203 expression suppressed BCL-2 protein and mRNA by western blotting and qRT-PCR analysis. Moreover, co-transfection experiments using a luciferase-based reporter assay demonstrated that mir-203 directly regulated BCL-2 expression and BCL-2 overexpression suppressed mir-203 mediated cell death. Knowledge gained through this profiling study can facilitate targeted therapeutic interventions. Citation Format: Bhavesh K. Ahir, Herbert H. Engelhard, Sajani S. Lakka. Elucidating the microRNA-203 specific biological processes in glioblastoma cells from high-throughput RNA-sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1424.