Hsa-miR-34a-5p Enhances Temozolomide Anti-tumoral Effects on Glioblastoma: In-silico and In-vitro Study

Glioblastoma multiform (GBM) is a commonly diagnosed brain neoplasm with a poor prognosis. Accumulating evidence has highlighted the significance of microRNA (miR) dysregulation in tumor development and progression. This study investigated the effect of hsa-miR-34a-5p and its combination with temozolomide on GBM, the related molecular mechanisms, and the signaling pathway using and approaches. The tumor bulk and single-cell RNA sequencing analyses were done on TCGA-GTEx, CGGA, GSE13276, GSE90603, and GSE182109 datasets. After selecting the A172 cell line, hsa-miR-34a-5p mimics were transfected, and the cell viability, migration, cell cycle, clonogenicity, and apoptosis of studied groups were studied using MTT, scratch, flow cytometry, colony formation, and Annexin V/PI assays. The mRNA expression of , , , , , , , , , , , , and was studied using qRT-PCR method. hsa-miR-34a-5p downregulated expression, as the signaling factor of the MAPK pathway. The combined treatment significantly downregulated the expression of , , and , leading to the inhibition of the MET/MAPK pathway compared to temozolomide. Besides exerting anti-tumoral effects on the cell viability, migration, cell cycle, apoptosis, and clonogenicity of A172 cells, its combination with temozolomide enhanced temozolomide anti-tumoral effect. Compared to temozolomide, the combined treatment significantly decreased , , , and expression. hsa-miR-34a-5p targets , as the signaling factor of the MAPK pathway, and potentiates the temozolomide anti-tumoral effect on A172 cells.