title: Functional SNP in stem of mir-146a affects Her2 status and breast cancer survival.
abstract: In-silico investigation suggested a common variant within stem of miR-146a-5p precursor (rs2910164, n.60C>G) associated with breast cancer (BC) phenotypes. Our aim was computationally predicting possible targets of miR-146a-5p and probable rs2910164 mechanism of action in expression of phenotypes in BC. Additionally, a case-control study was designated to examine experimentally the correlation of mir-146a rs2910164 variant and BC phenotypes. In this study, 152 BC subjects and healthy controls were genotyped using RFLP-PCR. Allelic and genotypic association and Armitage's trend tests were run to investigate the correlation between the alleles and genotypes and expressed phenotypes of BC. Bioinformatics analyses introduce regulatory function of miR-146a-5p in numerous signaling pathways and impact of allele substitution upon mir-146a stem-loop stability. Logistic regression data represented the C allele of rs2910164 (OR = 4.00, p= 0.0037) as the risk allele and associated with Her2-positive phenotype. In a similar vein, data revealed the correlation of the C allele and cancer death less than two years in BC patients (OR = 2.65, p= 0.0217). Ultimately, unconditional logistical regression models suggested log-additive model for inheritance manner of rs2910164 in either Her2 status or BC survival (OR = 5.64, p= 0.0025 and OR = 3.13, p= 0.019, respectively). Using bioinformatics connected association of Her2 status to altered function of miR-146a-5p in regulation of focal adhesion and Ras pathway. Furthermore, computations inferred the association between death phenotype and studied SNP upon specific target genes of miR-146a-5p involved in focal adhesion, EGF receptor, Ras, ErbB, interleukin, Toll-like receptor, NGF, angiogenesis, and p53 feedback loops 2 signaling pathways. These verdicts may enhance our perceptions of how mir-146a rs2910164 affect expressed phenotypes in BC, and might have potential implications to develop BC treatment in future.
authors.affiliation: Department of Biology, Division of Cellular and Molecular Biology, Nourdanesh University of Meymeh, Meymeh, Isfahan, Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Meshkat
authors.affiliation: Cellular and Molecular Biology Division, Biology Department, Faculty of Sciences, University of Isfahan, Isfahan, Iran.
authors.forename: Hamzeh Mesrian
authors.initials: HM
authors.lastname: Tanha
authors.affiliation: Biology Department, Genetics Division, Faculty of Sciences, University of Isfahan, Isfahan, Iran.
authors.forename: Marjan Mojtabavi
authors.initials: MM
authors.lastname: Naeini
authors.affiliation: Cellular and Molecular Biology Division, Biology Department, Faculty of Sciences, University of Isfahan, Isfahan, Iran.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghaedi
authors.affiliation: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Sanati
authors.affiliation: Department of Biology, Division of Cellular and Molecular Biology, Nourdanesh University of Meymeh, Meymeh, Isfahan, Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Meshkat
authors.affiliation: Biology Department, Biochemistry Division, Faculty of Science, Payame noor University of Taft, Yazd, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Bagheri
mesh_terms: D000483:Alleles; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D053263:Gene Regulatory Networks; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009690:Nucleic Acid Conformation; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; C542542:MIRN146 microRNA, human
keywords: Breast cancer; Her2; cancer death; functional SNP; mir-146a