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INTERNATIONAL CONGRESS OF

CancerGenetics

• AKT1 as a central hub gene in miR-424/503 cluster-regulated oncogenic networks in cervical cancer

• Akram Rahimi-Moghaddam,^1,* Nassim Ghorbanmehr,² Sedigheh Gharbi,³
  1. Alzahra University
  2. Alzahra University
  3. Shahid Bahonar University of Kerman
  
  
  
• Introduction: The miR-424/503 cluster, located on the X chromosome, is implicated in various gynecological disorders due to its dysregulation. Previous studies have demonstrated that the expression levels of several members of the miR-424/503 cluster are downregulated in cervical cancer, which is the fourth most prevalent cancer among women globally and is predominantly caused by persistent human papillomavirus (HPV) infection. This study employed bioinformatics analyses to investigate the role of the miR-424/503 cluster in cervical cancer.
• Methods: In the present study, the target genes of the miR-424/503 cluster (hsa-miR-424-3p, hsa-miR-424-5p, hsa-miR-503-5p, hsa-miR-542-3p, hsa-miR-542-5p, hsa-miR-450b-5p, hsa-miR-450a-5p, and hsa-miR-450a-2-3p) were computationally predicted utilizing the miRNet platform, and a protein-protein interaction (PPI) network was constructed via the STRING database. To identify hub genes within the network, a topological analysis was conducted using Cytoscape 3.10.3. Furthermore, a functional pathway enrichment analysis of the miR-424/503 cluster target genes was performed employing the DAVID bioinformatics tool.
• Results: A total of 1003 target genes for the miR-424/503 cluster were identified using miRNet. Pathway analysis demonstrated that the majority of these genes are involved in pathways associated with cancer, the PI3K-Akt signaling, and HPV infection. The findings also revealed that the PI3K-Akt signaling pathway is not only a major cancer-related pathway but also a central pathway involved in HPV pathogenicity. Based on PPI network analysis results, the AKT1 gene, a key component of the PI3K-Akt signaling pathway, exhibited the highest degree centrality and was considered a hub gene.
• Conclusion: This study revealed that the downregulation of the miR-424/503 cluster in cervical cancer is associated with the HPV infection pathway and key oncogenic pathways, particularly the PI3K-Akt signaling pathway. The findings highlighted the therapeutic potential of targeting the PI3K-Akt pathway, especially its pivotal component AKT1, in cervical cancer treatment strategies.
• Keywords: miR-424/503 cluster, AKT1, cervical cancer, PI3K-Akt signaling pathway, network analysis.