In Silco Study of MIR-124-1 Transcription Factors in Glioblastoma

MIR-124-1 is a brain-abundant MIRNA, whose expression is important for neuronal tissue division, growth and actions. However, expression of miR-124-1 regulatory mechanisms controlling its actions in neuronal cells in health and diseases still poorly addressed. To understand mechanism for transcriptional and functional regulation of miR-124 in neuronal and glioblastoma cells, this study combined gene expression profiling data and computational transcription factor and microRNA target predictions. The present research focuses on transcription factors and DNA methylation, which are central to miR-124-1 expression regulation. A core promoter sequence of miR-124-1 was predicted to be 500 bp and 100 bp, upstream and downstream of its transcription start sites. Seventy three binding sites of fifty transcription factors in promoter region were found, using MatInspector software. Among these transcription factors, MEIS1, POU3F2, SALL2, ETV1, and MAZ, are known to be brain-enriched transcriptional activators. By using omics data analysis, expression of MAZ, PLAG1 KLF2 as well as a transcriptional repressor ZNF239 showed significant correlation with decline in miR-124-1 expression in glioblastoma cells. Furthermore, a potential CpG island was reported in the promoter, providing another mechanism for transcriptional inhibition of miR-124. As miR-124-1 regulates a number of neuronal physiological and pathological processes, we made an attempt to define its potential targets. A computational prediction of miR-124-1 targets suggested 265 targets with two or more conserved seed sites. Pathway-based analysis of these target genes revealed a significant enrichment for axonal guidance and cancer signaling pathways. At least ten of these targets, SRGAP1, GNAI3, PLXNA3, SEMA5A, SEMA6A, CEBPA, CBL, RASSF5, MITF, and RPS6KB1, showed expected inverse correlation between their expression values and miR-124-1 suppression in glioblastoma cells. Taken together, our data form foundation of subsequent future validation researches for miR-124-1 expression regulation including transcription factors and CpG Island within its promoter as well as functional regulation comprising biological pathways controlled by its target genes.