The Association Between rs11671784 Polymorphism in pre-miR-27a and Lung Cancer
AbstractBackground: MicroRNAs are one of the most remarkable controlling agents of gene expression. MiR-27a is an important onco-miR which has an increased expressionand oncogenic role in many types of cancer through controlling tumor-suppressorgenes such as FOXO1, TP53, RYBP, and FADD. Moreover, it has a dual role insome types of cancer and decreased expression in some neoplasms, including nonsmallcell lung cancer (NSCLC) playing a tumor-suppressing role by controlling proto oncogenes such as IGF-1, EGFR, KRAS, PPFP, MYT1, and CYP1B1. Polymorphismsin pre-miRNA can affect miRNA processing and expression. There are twopolymorphisms “rs11671784” and “rs895819” within the loop region of pre-miR-27a. In 2013, the association between rs895819 and decreased expression of miR 27a alongside an increased risk of NSCLC was determined. Hence, the rs11671784polymorphism was selected for this study. This study aims to investigate the associationbetween the rs11671784 polymorphism within the loop region of pre-miR-27aand lung cancer susceptibility.Methods: This case-control study was conducted on genomic DNA from the blood samples of 110 healthy subjects and 70 patients collected from the Omid Hospital of Isfahan using the salting-out method. The genotype of rs11671784 was determined using appropriate primers and the Restriction Fragment Length Polymorphism (RFLP) technique. A statistical analysis was performed using the Power MarkerSPSS version-23 software and the SISA website.Results: This study proved that the presence of the T allele at the polymorphic position can reduce the risk of lung cancer up to 6.7 fold (OR=0.15, p=0.039, 95%CI=0.019-1.2), likely because of its effect in pre-miR-27a processing. In fact, onlyone patient was found with the T allele, compared to ten in healthy subjects, who was a smoker suffering adenocarcinoma. The U allele observed in the pre-miR-27a compared to the C allele, can reduce the free energy (ΔG) by 0.8 kcal/mol and stabilizethe structure, and accordingly, may lead to an increase in miR-27a.Conclusion: The present study examines the correlation between rs11671784 and lung cancer for the first time, which suggests that rs11671784 could be known as a biomarker for resistance to lung cancer among the studied population. However further studies are needed to determine the effect of this polymorphism on the expressionof miR-27a.
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