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.

MicroRNA-based regulation of Aurora A kinase in breast cancer

“…The process of carcinogenesis and therapeutic responses present a terrific challenge to favorable therapeutic outcome [41]. However, identifying cancer specific targets can pave the way for effective treatment options against specific cancer types [42]. Computational approaches are extensively used to investigate molecular and genetic mechanism of cancer progression by identifying lead genes and the abnormal regulatory pathways of disease [43].…”

A GNAS Gene Mutation’s Independent Expression in the Growth of Colorectal Cancer: A Systematic Review and Meta-Analysis

“…Worldwide, colorectal cancer (CRC) is a foremost contributor to cancer-related death annually and continues to pose a significant challenge to the world [ 1 ]. With reports of greater than 1.8 million new cases of CRC diagnoses and approximately 0.86 million deaths throughout the globe in 2018 [ 2 ], CRC is the third most frequently occurring cancer, and the third most common cause of cancer-associated deaths in both genders [ 3 ], representing 10% of all cancer diagnosed yearly [ 4 ]. Over the past decade, increasing evidence points to the role of G-protein activating subunit gene mutations in the development of tumours, i.e., CRC [ 5 ].…”

“…Several proteins, including those that are produced by the genes GNAS, GNAQ, GNA11 and GNA12 bind to G-protein-coupled receptors (GPCRs) and are essential for the transduction of cellular signals. The process for the initiation and progression of CRC stems from the accumulation of several aberrant genetic and epigenetic alterations in the epithelium cells of the colon and rectum [ 2 ]. Reports on overexpression of the GNAS gene in cancers and, linked with tumourigenesis metastasis and progression are vast [ 2 ]; however, the detailed understanding of the genetic contribution of GNAS mutation in colorectal cancer (CRC) progression remains ambiguous and unclear [ 2 , 3 , 6 ].…”

“…However, there is still a downside to this discovery, which is a limited clue to the GNAS gene role in the epigenetics of CRC diagnosis and progression [ 6 , 9 ]. An additional prominent downside to cancer sequencing research is the restricted statistical power to substantially recognize mutated genes that have a midway or lower rate of recurrence of mutation (e.g., 5% frequency) [ 2 ]. Considering the importance and functional contribution of the G-subunits genes in CRC progression, GNAS gene is among the top seven most frequently recognized mutated genes in tumourigenesis, such as in CRC; others include APC, KRAS, TCF7L2, epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGF1R) and CASP8 [ 2 ].…”

Curcumin Targeting Non-Coding RNAs in Colorectal Cancer: Therapeutic and Biomarker Implications

“…Therefore, it is urgent to find new therapeutic methods and develop effective biomarkers for the early diagnosis, treatment, and prognosis assessment of colorectal cancer to improve the survival status. Some studies have demonstrated that epigenetic mechanisms play a key role in cancer progression, particularly non-coding RNAs (ncRNAs) [ 9 ]. Indeed, many studies have demonstrated that the development pathogenesis of colorectal cancer is highly influenced by ncRNAs [ 10 ], the abnormal expression of oncogenic and tumor-suppressor molecules, and the abnormal activation of various cell signaling pathways [ 11 , 12 ].…”