Identification of critical microRNA gene targets in cervical cancer using network properties.

Abstract

miRNAs are short non-coding RNAs which function as oncogenes or tumour suppressor gene and regulate gene expression by controlling targets that play role in cancer development and progression. Numerous recent studies have established an association of abnormal expression of miRNA with cervical cancer progression. Although the number of reported deregulated miRNA in cervical cancer is increasing, only a few associations between miRNA and their targets have been studied in cervical cancer. Therefore, we performed a systematic analysis of known dysregulated miRNAs involved in cervical cancer so as to identify critical miRNA targets that could pave way for therapeutic solutions. In this study, miRNAs reported to be dysregulated in cervical cancer were collected and their targets predicted using TargetScan, PicTar and miRanda. These targets were subsequently compared with previously curated gene dataset involved in cervical cancer to derive the putative target dataset. We then compared network properties (composed of degree, betweenness centrality, closeness centrality and clustering coefficient) of the putative, validated and human protein-protein interaction network. Based on the topological properties genes were ranked and observed that the gene targets BIRC5 (survivin), HOXA1 and RARB presenting with high Novoseek score of Genecards were enriched in cervical cancer. BIRC5 is an anti- apoptotic protein while HOXA1 and RARB are transcription factors which play critical role in altering the level of cell cycle and apoptosis associated proteins. Also, miRNA-mRNA network was constructed and it was found that miR-203 and miR-30b could target these genes. The analysis indicates that the genes BIRC5, HOXA1 and RARB are critical targets that play an important regulatory role in cervical cancer pathogenesis.