Presence of the minor allele of microRNA205 rs3842530 polymorphism increases 18FDG uptake in patients with breast cancer via targeting VEGF

Abstract

MicroRNAs (miRNAs) are regarded as key regulators of gene expression involved in the pathogenesis of various diseases. Numerous single nucleotide polymorphisms (SNPs) in miRNA genes have been found to be associated with human diseases by affecting the processing process of miRNAs. In the present study, patients with breast cancer underwenta PET scan, and the maximum standard uptake value (SUVmax)/partial volume-corrected standard uptake value (SUVpvc) were determined in each individual. The samples were collected and genotyped for rs3842530. Statistical analysis was performed to evaluate the difference between the genotype groups. The results demonstrated that miR-205 downregulated the expression of vascular endothelial growth factor (VEGF) by binding to its 3'untranslated region. The introduction of exogenous miRNA, which mimicked miR-205, decreased the protein and mRNA expression levels of VEGF and, consistently, the suppression of endogenous miR-205 resulted in an increase in the expression levels of VEGF. Furthermore, it was found that the expression of mature miR-205 was markedly reduced by the presence of rs3842530. 18F-fluorodeoxyglucose (18FDG) metabolism, including SUVmax and SUVpvc, are important parameters of PET, and dysregulation of the expression of VEGF has been reported to be associated with an altered 18FDG metabolism. In the present study, it was found that the presence of minor allele rs3842530 was correlated with increased SUVmax and SUVpvc, which may have been mediated by release of the physiologically inhibited expression of VEGF. Therefore, VEGF was a direct target of miR-205, and the presence of rs3842530 compromised the expression of miR-205, suggesting it is a promising biomarker for the metabolism of 18FDG.