Title:Identification of Critical MicroRNA Gene Targets in Cervical Cancer Using Network Properties
Volume: 3
Issue: 1
Author(s): Garima Sharma and Subhash M. Agarwal
Affiliation:
Keywords:
Cervical cancer, cervical cancer gene database, miRNA, network properties, oncogenes, protein interaction
networks.
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.
