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Association Between microRNA-125a rs12976445 C>T Polymorphism and 18F-Fluorodeoxyglucose (18FDG) Uptake: Clinical and Metabolic Response in Patients with Non-Small Cell Lung Cancer

Zhina Zang, Wenhua Guan, Diansen Chen, Yan Han, Zhan Shi, Jinjin Zhou

Department of Nuclear Medicine, The Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China (mainland)

Med Sci Monit 2016; 22:4186-4192

DOI: 10.12659/MSM.897255

Available online:

Published: 2016-11-04

BACKGROUND: MicroRNA-125a (miR-125a) has been involved with many diseases, such as hepatocellular carcinoma and inflammation. In this study, we aimed to investigate the molecular mechanism, including the potential regulator and signaling pathways, of vascular endothelial growth factor (VEGF).
MATERIAL AND METHODS: We divided the participants into 3 groups by rs12976445 genotype and performed chi-square tests to evaluate the differences between CC and CT+TT groups for sex, age, grading, pT category, metastases, and fludeoxyglucose F18 injection (18FDG) metabolism.
RESULTS: We found all variables to be statistically significant. We searched the miRNA database online (www.mirdb.org) with the “seed sequence” located within the 3-prime untranslated region (3’ UTR) of the target gene and then validated VEGF to be the direct gene via luciferase reporter assay system. We also established the negative regulatory relationship between MiR-125a and VEGF by studying the relative luciferase activity. We conducted real-time polymerase chain reaction and Western blot analysis to study the mRNA and protein expression level of VEGF among different groups (CC=18, CT=8, TT=3) or cells treated with scramble control, miR-125a mimics, VEGF RNA, and MiR-125a inhibitors.
CONCLUSIONS: We validated the negative regulatory relationship between MiR-125a and VEGF and found that rs12976445 may function as a biomarker to predict metabolism of 18FDG.

Keywords: Carcinoma, Non-Small-Cell Lung - metabolism, Base Sequence, A549 cells, Demography, Fluorodeoxyglucose F18 - metabolism, Gene Expression Regulation, Neoplastic, Genes, Reporter, Genetic Association Studies, Genetic Predisposition to Disease, Luciferases - metabolism, Lung Neoplasms - metabolism, MicroRNAs - metabolism, Polymorphism, Single Nucleotide - genetics, Transfection, Vascular Endothelial Growth Factor A - genetics