miR-770 as a potential regulator of DNA methylation-related gene expression in glioblastoma: from in silico prediction to functional validation

Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain tumors, in part due to its molecular heterogeneity and dysregulated epigenetic landscape. In this study, the potential tumor-suppressive role of miR-770 and its association with aberrant DNA methylation in GBM was investigated. Using bulk RNA sequencing data from The Cancer Genome Atlas and The Genotype-Tissue Expression, we performed differential expression analysis and introduced a set of genes as methylation-related differentially expressed genes (methylation-DEGs); these are genes involved in DNA methylation and differentially expressed in GBM. Subsequently, employing weighted gene co-expression network analysis, miR-770 was identified as a key microRNA in DNA methylation in GBM progression. Expression analysis confirmed the downregulation of miR-770 in GBM tissues and its co-expression with methylation-related genes, including DNMT1 , UHRF1 , PCNA , and HDAC1 . Functional assays in the U251 glioma cell line revealed that miR-770 overexpression led to reduced cell proliferation, migration, and invasion, while promoting apoptosis. Notably, the co-expression of miR-770 with methylation-related genes was also validated in U251 cells. Taken together, our findings suggest that miR-770 represent a regulator of DNA methylation-related gene expression networks in GBM.