Bioinformatics analysis of hsa-miR-۱۳۵a on APC gene in patients with Familial Adenomatous Polyposis

Familial Adenomatous Polyposis (FAP) is an autosomal-dominant inherited disease caused by germlinemutations in the Adenomatous Polyposis Coli (APC) gene. Locating on choronosome ۵, the APC geneencodes a tumor suppressor protein that acts as an antagonist in Wingless-Related Integration Site (WNT)signaling pathway. Defects in this gene cause FAP that usually results to malignancy. The aim of our studywas to find bioinformatics information about the role of APC gene in the process of FAP. For this purpose,GEO datasets was studied in order to achieve information about APC gene, miRdSNP was applied to choosemicroRNA involved in FAP disease. The miRBase database helped to detect data about selected microRNA.The pathways associated with APC were detected through sortment of genes in DAVID database. Theinformation about APC gene in the carcinogene pathway was obtained from KEGG pathways. The resultsshowed that hsa-miR-۱۳۵a is predicted to target the APC gene. It targets the ۳’UTR region of APC,suppresses its expression. Inactivation of the APC gene is a major initiating event in colorectal tumorigenesis.Based on the findings, it is inferred that β-catenin levels may increase due to the cessation of APC genefunction. Since the WNT signaling pathway is a conserved pathway, tumorigenesis may begin because ofincorrect signaling of the WNT pathway. APC-free β-catenin provokes the WNT signaling pathway as aprotein, leading to active transcription of target genes. Also we saw SNP:rs۶۸۷۵۸۹۴ (single nucleotide changec/t conversion) in nucleotide ۱۴۱ on miR-۱۳۵a sequence which had no effect on the emrgene of this disease.Itis concluded that as APC is a tumor suppressor gene so it is not the cause of the disease and when its functionis stopped by miR-۱۳۵a , the cell progresses to tumorigenesis.

Keywords:

FAP , miRNA , SNP , KEGG , DAVID