Mouse Anti Human aminopeptidase N Hybridoma [ICC4/264/74]

Background: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. Methods: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. Results: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. Conclusions: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.

Background and aims: Atherosclerosis is an inflammatory cardiovascular disorder characterized by accumulation of lipid-loaded macrophages in the intima. Prolonged accumulation leads to apoptosis of macrophages and eventually to progression of lesion development. Prevention of macrophage accumulation within the intima has been shown to reduce lesion formation. Since CD13 mediates trafficking of macrophages to sites of injury and repair, we tested the role of CD13 in atherosclerosis. Methods: CD13(+/+) Ldlr(-/-) and CD13(-/-) Ldlr(-/-) (low density lipoprotein receptor) mice were fed basal or high fat diet (HFD) for 9, 12 and 15 weeks. Mice were euthanized and aortic roots along with innominate arteries were analyzed for atherosclerotic lesions. Cellular mechanisms were determined in vitro using CD13(+/+) and CD13(-/-) bone marrow derived macrophages (BMDMs) incubated with highly oxidized low-density lipoprotein (oxLDL). Results: At the 9 and 12 week time points, no differences were observed in the average lesion size, but at the 15 week time point, CD13(-/-) Ldlr(-/-) mice had larger lesions with exaggerated necrotic areas. CD13(+/+) and CD13(-/-) macrophages endocytosed similar amounts of oxLDL, but CD13(-/-) macrophages generated higher amounts of oxidative stressors in comparison to CD13(+/+) macrophages. This increased oxidative stress was due to increased nitric oxide production in oxLDL treated CD13(-/-) macrophages. Accumulated oxidative stress subsequently led to accelerated apoptosis and enhanced necrosis of oxLDL treated CD13(-/-) macrophages. Conclusions: Contrary to our prediction, CD13 deficiency led to larger atherosclerotic lesions with increased areas of necrosis. Mechanistically, CD13 deficiency led to increased nitric oxide production and consequently, greater oxidative stress.