Genomic profiling of microRNA target genes in colorectal cancer.

Abstract

Colorectal cancer is the second and third most common cancer in men and women, respectively, worldwide. Alterations such as genetic and epigenetic are common in colorectal cancer and are the basis of tumor formation. The exploration of the molecular basis of colorectal cancer can drive a better understanding of the disease as well as guide the prognosis, therapeutics, and disease management. This study is aimed at investigating the genetic mutation profile of five candidate microRNAs (hsa-miR-513b-3p, hsa-miR-500b-3p, hsa-miR-500a-3p, hsa-miR-450b-3p, hsa-miR-193a-5p) targeted by seven genes (APC, KRAS, TCF7L2, EGFR, IGF1R, CASP8, and GNAS)) using in silico approaches. Two datasets (dataset 1 from our previous study and dataset two (The Cancer Genome Atlas, Nature 2012) were considered for this study. Protein-protein interaction, expression analysis, and genetic profiling were carried out using STRING, FireBrowse, and cBioPortal, respectively. Protein-protein interaction network showed that epidermal growth factor receptor has the highest connection among the target genes and this can be considered as the hub gene. Relative to other solid tumors, in colorectal cancer, six of the target genes were downregulated and only CASP8 was upregulated. Genes with protein tyrosine kinases domain were frequently altered in colorectal cancer and the most common alteration in these genes/domain are missense mutation. These results could serve as a lead in the identification of driver genes responsible for colorectal cancer initiation and progression. However, the intense mechanism of these results remains unclear and further experimental validation and molecular approaches are the focal points in the nearest future.