Functional role of hub molecules in miRNA and transcription factor mediated gene regulatory network of colorectal and lung cancer

Abstract

MicroRNAs (miRNAs) have the ability to upregulate and downregulate different biological processes by altering the gene expression at post-transcriptional level which leads to different kinds of diseases including cancer. In this study, we analysed the properties and role of different miRNAs involved in colorectal and lung cancer. The sequence composition characteristics, length distribution, GC percentage comparison for both mature and premature miRNAs and the frequencies of the nucleotides at the seed region of miRNAs were measured. The study showed that purine and pyrimidine bases have a role in upregulation and downregulation of miRNA in cancer. Network analysis of up- and down-regulated miRNAs and their target genes showed hsa-mir-21-5p to be up-regulated in both cancers and targeting the gene PTEN. The co-expressed target gene modules involved in both cancers were also compared. Further, we identified the miRNA targets which are also regulated by the transcription factors. The analysis revealed potential novel miRNA biomarkers such as hsa-miR-106b-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-140-5p, hsa-miR-20a-5p, hsa-miR-196a-5p, hsa-miR-17-5p, hsa-miR-95-3p and hsa-miR-146a-5p. The target genes of these miRNAs - CDKN1A, CCND1, VEGFA regulated by a large number of transcription factors, reported as cancer biomarkers. Transcription factors such as SP1, STAT3, TP53 and RE1A regulate a number genes in both lung and colorectal cancers and are reported to be involved in cancer pathways. Thus, the important hub molecules and miRNAs identified here can be modulated to prevent cancer progression and to detect the diseases early.