Article type: Research Article
Authors: Meshkat, Mahboobeha | Tanha, Hamzeh Mesrianb | Naeini, Marjan Mojtabavic | Ghaedi, Kamranb; * | Sanati, Mohammad H.d | Meshkat, Marzieha | Bagheri, Fatemehe
Affiliations: [a] Department of Biology, Division of Cellular and Molecular Biology, Nourdanesh University of Meymeh, Meymeh, Isfahan, Iran | [b] Cellular and Molecular Biology Division, Biology Department, Faculty of Sciences, University of Isfahan, Isfahan, Iran | [c] Biology Department, Genetics Division, Faculty of Sciences, University of Isfahan, Isfahan, Iran | [d] National Institute of Genetic Engineering and Biotechnology, Tehran, Iran | [e] Biology Department, Biochemistry Division, Faculty of Science, Payame noor University of Taft, Yazd, Iran
Correspondence:
[*]
Corresponding author: Kamran Ghaedi, PhD. of Molecular and Cellular Genetics, Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan 81746-73441, Iran. Tel.: +98 31 37932479; Fax: +98 31 37932456; E-mail:kamranghaedi@yahoo.com, kamranghaedi@sci.ui.ac.ir
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.
Keywords: Breast cancer, cancer death, Her2, mir-146a, functional SNP
DOI: 10.3233/CBM-160633
Journal: Cancer Biomarkers, vol. 17, no. 2, pp. 213-222, 2016
