The impact of rs9341070 and miR-122 interaction on ESR1 gene through Breast cancer
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Zeinab Badihyan Najafabadi,1 Romina Ali Akbarzadeh,2 Pegah Javid,3 Mansoureh Azadeh,4,*
1. Zist Fanavari Novin Biotechnology Department, Provincial Technical and vocational Training Organization, Isfahan, Iran
2. Zist Fanavari Novin Biotechnology Department, Provincial Technical and vocational Training Organization, Isfahan, Iran
3. Zist Fanavari Novin Biotechnology Department, Provincial Technical and vocational Training Organization, Isfahan, Iran
4. Zist Fanavari Novin Biotechnology Department, Provincial Technical and vocational Training Organization, Isfahan, Iran
- Introduction: Breast cancer is the most common malignancy among women worldwide. Genetic alterations, including Single Nucleotide Polymorphisms (SNPs) have been identified as important factors in understanding carcinogenesis. Numerous studies have shown their association with microRNA binding. MicroRNAs bind to 3'UTR of target mRNAs, blocking translation or, in rare cases, destroying target mRNAs and regulate various biological processes such as cell differentiation, cellular metabolism, immune response, and apoptosis. Since the expression level of miRNAs varies between normal and cancer cells, they are proposed as clinical biomarkers and even therapeutic targets in cancers. The aim of this study was to investigate the effect of SNP:rs9341070 on has-miR-122-5p binding to Estrogen Receptor Alpha (ESR1) gene and its suppressive function.
- Methods: To perform this study, the desired gene was selected through literature mining of previous studies. The NCBI database was used to obtain more information about SNP: rs9341070. The miRdSNP database was also used to investigate the association between rs9341070, ESR1 gene and has-miR-122-5p in breast cancer. In the following, the miRNASNP-v3 database was applied to study the presence of rs9341070 in 3´-UTR region of ESR1 gene and its interaction with the has-miR-122-5p. Through the studies, the gene, SNP and microRNA, were selected as ESR1, rs9341070, and has-miR-122-5p respectively.
- Results: The results from research in databases showed that the occurrence of rs9341070 in ESR1 3´-UTR region is a risk factor in breast cancer. The hsa-miR-122-5p is a tumor suppressor and inhibits cancer cell proliferation and tumorigenesis in breast tissue. The has-miR-122-5p binds to mRNA and prevents the expression of ESR1 gene. Occurrence of rs9341070 at the seed match of miR to ESR1 gene by converting the C to T makes the miRNA to lose the mRNA. It makes an increase in ESR1 gene expression and tumorigenesis in this tissue. The rs9341070 prevents the binding of miR-122 to ESR1 gene in breast tissue. As a result, the function of tumor suppression and inhibition of cancer cell growth is impaired. It results in upregulation in ESR1 and progression of breast cancer.
- Conclusion: According to the findings, the occurrence of SNPs in 3'-UTR disrupts the regulatory action of microRNAs on target mRNAs and potentially contribute to cancer and other chronic diseases. The rs9341070 is associated with various aspects of breast cancer and plays an important role in preoperative assessments as a marker in predicting the progression of breast cancer metastasis. The microRNAs can also potentially be predictive as therapeutic biomarkers that allow patients to benefit from personalized medicine. Our study showed that miR-122 expression level and its interaction with ESR1 gene play important roles in inhibiting tumorigenesis, development and progression of breast cancer and may be used as a biomarker for diagnosis and prognosis and even a target for breast cancer treatment. However, experimentally researches are needed to confirm these results in patients with breast cancer.
- Keywords: Cancer, 3’UTR, MicroRNA, SNP
