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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.

ABSTRACT: 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.

SUBMITTER: Zang Z

PROVIDER: S-EPMC5100836 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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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.

Zang Zhina Z Guan Wenhua W Chen Diansen D Han Yan Y Shi Zhan Z Zhou Jinjin J

Medical science monitor : international medical journal of experimental and clinical research 20161104

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 ...[more]

PMID: 27814341

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Project description:Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n?=?109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ?25?mm Hg (P?=?0.013, P?=?0.006, P?=?0.049, P?=?0.002, P?=?0.68, respectively) and with PVR ?480?dyn·s/cm (P?<?0.001, P?=?0.045, P?<?0.001, P?<?0.001, P?=?0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r?=?0.55, r?=?0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.

Dataset Information

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.

Publications

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.

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