In silico detection of a new deleterious single nucleotide polymorphism and miRNA related to CHEK۲ gene in breast cancer and their interactions

Introduction: Checkpoint Kinase ۲ (CHEK۲) is a serine/threonine protein kinase that acts as a tumorsuppressor gene through the induction of cell cycle checkpoint, the inhibition of cellular proliferation, andthe activation of DNA repair pathways and apoptosis. Although CHEK۲ mutations are rare, it reported thatthe risk of developing breast cancer is higher in carriers of truncating mutations. We also propose thatdeleterious single nucleotide polymorphism (SNPs) in ۳ ׳-UTR of the CHEK۲ gene may affect the interactionof microRNAs (miRNAs) that regulate the expression of this gene in breast cancer. Therefore, this in silicostudy was conducted to identify the possible deleterious single nucleotide polymorphisms (SNPs) in the ۳ -׳UTR of the CHEK۲ gene and also miRNAs that target it. Moreover, we aimed to investigate the influence ofthe identified SNPs on binding of the miRNAs in the ۳ ׳-UTR of CHEK۲ gene.Methods: The CHEK۲ gene sequence was obtained from NCBI database. The dbSNP tool of NCBI was alsoused to identify the possible deleterious SNPs in the gene. Next, integrated bioinformatics data analysis bymiRWalk, PhenomiR, miRBase, David, and miRNASNP-V۳ were performed to identify miRNAs that targetCHEK۲ gene mRNA and also to evaluate the effect of SNPs on its binding site.Results: Our results introduced rs۵۴۰۴۱۰۴۵۱ as a deleterious SNP that result to the substitution of G to Aallele in CHEK۲ gene of breast cancer patients. It also found that hsa-miR-۱۲۱۳۶ may regulate CHEK۲ geneexpression. Moreover, in silico data analysis indicated that rs۵۴۰۴۱۰۴۵۱ may affect the performance andbinding of hsa-miR-۱۲۱۳۶ in the ۳'-UTR of the CHEK۲ mRNA.Conclusion: This study for the first time, introduces rs۵۴۰۴۱۰۴۵۱ and hsa-miR-۱۲۱۳۶ as importantbiomarkers that may be associated with CHEK۲ gene and breast cancer. However, experimental studies areneeded to confirm the results of this study