Association between genotype of miR-4270 binding site within 3 -UTR of ERCC1 gene and some clinicopathological features of breast cancer patients

Introduction: One of the Effective factors in management of breast cancer (BC) is early diagnosis. The involvement of deregulated miRNA networks in cancer progression is validated in several studies. MicroRNAs control expression of gene by binding to their regulatory regions (UTR). A SNP within a miRNA binding site or recognition element (MRE) could change mRNA level and protein. ERCC1 (gene ID: 2067) is involved in the Nucleotide excision repair (NER). This signaling pathway is associated with BC. In present study, we genotyped 3 -UTR ERCC1 and evaluated staging in BC patients in Markazi province.Method: The 3 -UTR of ERCC1 were analyzed for MRE sites using bioinformatics software. In present case-control study, 45 BC samples were evaluated by digestion method. Two selected miRSNPs were genotyped with MboII and AvaII. Results: Bioinformatics analysis showed that the restriction sites of aforementioned enzymes in the 2342bp 3 -UTR of ERCC1 are related to MRE of miR-4270 and miR-2355. These bindings have negative ΔΔG (-0.07& -.002). Electrophoresis indicated accuracy of PCR-RFLP reaction. Also, the positive correlation of MRE change of miR-4270 (homozygote TG) with metastasis and grade of the tomur was confirmed statistically (95% CI, P:0.03).Conclusion: Several SNPs have been implicated in genetic susceptibility of BC. Studies have shown that deregulation of ERCC1 is associated with resistance to chemotherapy and ionizing radiation. We confirmed association between MRE nucleotide changes of miR-4270 within 3 -UTR ERCC1 with tumor-staging. This change could be used as a diagnostic biomarker for risk and progression of BC and response to treatment probably.

کلیدواژه ها:

Breast Cancer ، ERCC1 ، 3 -UTR ، miRSNP ، Biomarker