miRNA SIGNATURES AND CONTRIBUTION TO FAMILIAL COLORECTAL CANCER: AN IN SILICO APPROACH


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Omnia Yousif1,Suleiman Suleiman2,Muntaser Ibrahim3
1Institute of Endemic Diseases,2Suba University Hospital,3Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum

Abstract

Background

BACKGROUND:  miRNAs are involved in carcinogenesis and tumor progression by regulating post-transcriptional gene expression. However, the miRNA regulatory networks in colorectal cancer (CRC) are far from being fully understood. Moreover, EBV rule in cancer and it is relation to miRNA was reported before. The objectives of this study were to identify the CRC miRNAs binding sites and their target mRNAs and it is relation to EBV virus.

METHODS: Whole exome sequence of one CRC family (2 cancers, 3 controls) was conducted. Depending on the fact that 80% of the miRNAs are located in the 3’ UTR variants, all 3’ UTR regions were analyzed using (polymiRTS, DIANA miRPath and CoMeTA tool)   databases.  We used another approach in which dysfunctional genes were analyzed for regulatory miRNA using miRwalker. In addition, PCR and in situ hyperdization of EBV was done to the same samples.

RESULTS: miRNA binding sites were predicted to be frequently affected in the genes (GTPBP5, VWDE and WWOX) targeted by (has-miR-29, has-miR- 130a-5p, has-miR23a-3p). These binding sites show the highest Context+ score change. has-miR29 was identified as a candidate based on Mirwk 2.0 and was association with CRC using DIANA miRPath tool (p= 0.0006).   In addition, PCR and in situ hyperdization show week signal of EBV virus in tumor samples.

CONCLUTION: Considering the complexity of cancer and the exome analysis of members of this family reported earlier miRNA appear to add yet a different layer of regulation that complements and intersects with other layers and networks towards the ultimate carcinogenesis goals and phenotypes. EBV is suggested play a major role together with miRNA-29 in the carcinogenesis process of CRC. Our results indicate that miRNAs and miRNAs binding sites, are potentially, identifying therapeutic targets for CRC.