Integrated bioinformatics analysis of miR-497/195 cluster network in cervical carcinoma

The miR-497/195 located at 17p13.1 is a highly conserved miRNA cluster whose abnormal expression is emerging as a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 to determine the prognostic utility and its role in cervical cancer (CC) using publicly available datasets. The in-silico analysis and validation identified the cluster as downregulated in CC. A total of 60 target genes were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for in silico functional enrichment, PPIN networks, hub gene identification, immune infiltration correlation, histopathological expressions, and metastatic potential of miR-497/195-5p and their target genes. The PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as top 10 hub genes (HGs). Further, miR-497-5p, RCAN3, RECK, OSBPL3, ATD5, BCL2, and HIST1H3H were shown to affect the overall survival in CC. We have identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 with metastatic potential. Besides 8 druggable genes targeted by 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.