Analysis of miR-497/195 cluster identifies new therapeutic targets in cervical cancer

Abstract

Abstract Objective miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets. Results In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 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.