Analysis of differentially expressed miRNAs targeting mitochondrial apoptosis genes in glioblastoma compared to astrocytoma

Glioblastoma (GBM) is the metastatic stage of astrocytoma (ATC) in which several pathways act in a tumorigenic role, including apoptosis, regulated by other underlying mechanisms and molecules such as microRNAs (miRNAs). The aim of this study was to search for differentially expressed miRNAs (DEMs) in GBM when compared to ATC that may be related to the role of apoptosis. miRNAs targeted by apoptosis genes were selected using miRTargetLink 2.0. Apoptosis genes were selected from the MitoXplorer 2.0 platform, with the main aim of analyzing genes from the intrinsic (mitochondrial) pathway. Thus, differential expression analysis (DEA) was performed on 155 GBM samples and 194 ATC samples from TCGA in the R environment to check for differentially expressed miRNAs (DEMs) related to apoptosis genes. We subdivided those that are strongly validated according to miRTargetLink and both strong and weak validation. Three DEMs strongly validated were upregulated (hsa-miR-210, hsa-miR-221, and hsa-miR-145), but none were downregulated. In the broader search, besides the three DEMs highlighted, it is worth mentioning the upregulated hsa-miR-27b, while three were found to be downregulated (hsa-miR-657, hsa-miR-573, and hsa-miR-7158). The target gene in common between the four upregulated DEMs is BNIP3, a pro-apoptotic gene, suggesting a suppression of the mitochondrial apoptotic pathway in GBM compared to ATC. Regarding the downregulated genes, no common target genes were found. Thus, in addition to indicating seven target miRNAs to be studied, our work also indicates a target gene that may be correlated with a dysregulation of apoptotic activity in GBM.