Integrated bioinformatic analysis of miR-15a/16-1 cluster network in cervical cancer

Abstract

The miR-15a/16-1 cluster is abnormally expressed in cervical cancer (CC) tissues and plays a vital role in cervical carcinogenesis. We aimed to evaluate the miR-15a/16-1 expression in healthy and cancerous cervical tissues, identify the associated networks, and to test its prognostic significance. miR-15a/16-1-MC expressions were analyzed in TCGA-CESC datasets by UALCAN, GEPIA2, and Datasetviewer. miR-15a/16-1 validated targets were extracted from mirTarBase and in silico functional analysis of the target genes were performed using WebGestalt. The interaction networks were constructed by the miRNet, STRING, and NetworkAnalyst tools. The prognostic significance and metastatic potential of the target genes were predicted using UALCAN and HCMDB. The FDA approved drugs to target miR-15a/16-1 and target gene network in CC were performed using DGIdb, STITCH and PanDrugs. TCGA-CESC and GEO data analysis suggested significant overexpression of miR-15a/16-1 in CC samples. The Kaplan-Meier survival analysis showed that miR-15a and its four target genes (BCL2, CCNE1, NUP50, and RBPJ) influence the overall survival of CC patients. Among the 66 differentially expressed target genes, 12 of them are linked to head, neck, or lung metastasis. Functional enrichment analysis predicted the association of this cluster with p53 signaling, human papillomavirus infection, PI3-AKT signaling pathway, and pathways in cancer. Drug-gene interaction analysis showed 52 potential FDA approved drugs to interact with the miR-15a/16-1 target genes. Nine of the 52 drugs are currently used as a chemotherapeutic agent for the treatment of CC patients. The present study shows that miR-15a/16-1 expression can be used as a clinical marker and target for therapy in CC.