Bioinformatics Evaluation of the Target Signaling Pathways and Function of Hsa-Mir-221-3p on Rs2603751 Snp Within Nr4a1 Gene, Associated With Triple-Negative Breast Cancer

Background and aim: breast cancer poses a major threat to women's health. triple-negative breast cancer (tnbc), which does not express estrogen α, progesterone and human epidermal growth factor 2 receptors, comprises 15% of all breast carcinomas. nuclear receptor 4a1 (nr4a1) is a member of nr4a orphan nuclear receptor superfamily. translocation of the protein from the nucleus to mitochondria induces apoptosis. the role of nr4a1 in cancer is currently controversial which could be specific to the types or subtypes of cancers. besides research confirming the oncogenic role, several studies have reported nr4a1 as a tumor suppressor. for instance, induced up-regulation of nr4a1 in hepatocytes, leading to the activation of p53, also nr4a1 expression has been reduced in tnbc. in the present study, we aimed to investigate non-coding snp polymorphisms in nr4a1 gene which probably influence gene expression in p53 activation pathway.methods: online target prediction tools including mirnasnp2 database were used to identify target snps that possibly regulated by micrornas so mirna hsa-mir-221-3p predicted to target the rs2603751 snp located on 3’utr of nr4a1 gene. the frequency of rs2603751 snp and the confirmation of hsa-mir-221-3p activity were respectively investigated by ncbi and mirbase. mirwalk 2.0, was used to predict target genes for the hsa-mir-221-3p. the signalling pathways of nr4a1 and hsa-mir-221-3p, were investigated by david and kegg databases.results: since rs2603751 is located in the 3utr region of the nr4a1 gene, the binding site of this microrna is precisely the rs2603751 polymorphism region, targeting this polymorphism can regulate nr4a1 gene expression in the cancer signalling pathway. regarding analysis based on mirnasnp2, it is predicted that hsa-mir-221-3p has the less binding affinity to the wild allele (t) than the mutant rs2603751 allele. due to negative regulatory function of hsa-mir-221-3p, it is expected that the expression of the wild allele of the target gene will be increase and eventually, the p53 signalling pathway becomes more active and more apoptosis occurs.conclusion: in conclusion, hsa-mir-221-3 may regulate nr4a1 gene that is vital for tnbc development and progression, hsa-mir-221-3 and targeting the mutant allele (rs2603751), could be as potential biomarkers and therapeutic targets for targeted therapy of tnbc.