Integrated transcriptomics and miRNA-mRNA network analysis reveals Kisspeptin-10 mediated regulation of EMT and...

Glioblastoma multiforme (GB) is the most aggressive and lethal primary brain tumor, with limited biomarkers for diagnosis and therapeutic targeting. This study aimed to investigate the regulatory effects of Kisspeptin-10 on epithelial-mesenchymal transition (EMT) and apoptosis in GB by integrating transcriptomic profiling, network analysis, and in-vitro validation. Kisspeptin-10, a metastasis-suppressor peptide known to modulate EMT and apoptotic pathways in several cancers, has not been previously explored in GB. Differentially expressed genes (DEGs) were identified from publicly available GEO datasets using limma, followed by STRING-based protein-protein interaction (PPI) analysis, cytoHubba-based hub gene ranking, and construction of miRNA-mRNA regulatory networks. A total of 1401 DEGs were identified, including 859 upregulated and 542 downregulated genes, enriched in pathways associated with EMT regulation, cell-cycle progression, extracellular matrix remodeling, and apoptosis. Hub genes such as CDK1, CDC20, JUN, and FABP5 were identified, while miR-200, miR-345, and miR-577 emerged as key regulatory miRNAs linked to EMT and apoptotic signaling. In-vitro validation further supported the modulatory effects of Kisspeptin-10 on EMT and apoptosis markers in GB cells. These findings highlight the diagnostic and therapeutic relevance of Kisspeptin-10-associated molecular regulation in GB. This is the first study to integrate transcriptomics, miRNA-mRNA network analysis, and experimental validation to elucidate Kisspeptin-10-mediated modulation of GB progression.