Cochranetimmermann1387

The long non-coding RNA (lncRNA) H19 acts as a competitive endogenous RNA (ceRNA) of miR-29b-3p and has been reported to exert pro-tumorigenic roles in several cancer types. However, the role of lncRNA H19 in lung cancer is not fully understood. Here, we investigated the role of the lncRNA H19/microRNA-29b-3p (miR-29b-3p)/high mobility group box 1 (HMGB1) signaling pathway in lung cancer cell growth using 293T, NCI-H1975, Calu-3 and 2BS cell lines. Cell viability was determined using a cell counting kit-8 (CCK-8) assay, while apoptosis and cell cycle distribution were assessed by flow cytometry. Cell migration was detected using a wound healing assay. Cell invasion was evaluated by transwell assay. The expression of lncRNA H19, miR-29b-3p, HMGB1, toll-like receptor 4 (TLR4), and matrix metallopeptidase 9 (MMP-9) was measured by fluorescence quantitative PCR or western blotting. We demonstrated that miR-29b-3p could directly bind to both lncRNA H19 and HMGB1 by dual-luciferase reporter assay. Three shRNAs targeting lncRNA H19 (shlncRNA H19) were designed, and shlncRNA H19-2 was selected to investigate the function of lncRNA H19 in tumor cell biology. Compared with controls, lung cancer cells expressing shlncRNA H19 exhibited decreased proliferation, cell-cycle arrest at the G1 phase, increased levels of cell apoptosis, and reduced migration and invasion. Moreover, shlncRNA H19 upregulated the expression of miR-29b-3p and reduced the protein expression of HMGB1, TLR4, and MMP-9 in lung cancer cells. Together, our data indicate that the lncRNA H19/miRNA-29b-3p/HMGB1 signaling axis is involved in the regulation of lung cancer cell growth.HLA-B*440268 differs from B*44020101 by one synonmous nucleotide substitution in codon-10 GGG->GGA This article is protected by copyright. All rights reserved.The clinicopathological implication and prospective molecular mechanisms of miRNA-145-5p in the metastasis of prostate cancer (PCa) stand unclear. Herein, it is found that miRNA-145-5p expression was remarkably reduced in 131 cases of metastatic PCa than 1371 cases of localised ones, as the standardised mean differences (SMD) was -1.26 and the area under the curve (AUC) was 0.86, based on miRNA-chip and miRNA-sequencing datasets. The potential targets of miRNA-145-5p in metastatic PCa (n = 414) was achieved from the intersection of miRNA-145-5p transfected metastatic PCa cell line data, differential expression of metastatic PCa upregulated genes and online prediction databases. TOP2A was screened as one of the target hub genes by PPI network analysis, which was adversely related to miRNA-145-5p expression in both metastatic PCa (r = -0.504) and primary PCa (r = -0.281). Gene-chip and RNA-sequencing datasets, as well as IHC performed on clinical PCa samples, showed consistent upregulated expression of TOP2A mRNA and protein in PCa compared with non-PCa. The expression of TOP2A mRNA was also significantly higher in metastatic than localised PCa with the SMD being 1.72 and the AUC of sROC being 0.91. In summary, miRNA-145-5p may participate in PCa metastasis by binding TOP2A and be useful as a biomarker for the detection of metastatic PCa.Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a hereditary, deteriorating central nervous disease in horses. Currently, the only way to confirm eNAD/EDM is through a postmortem histological evaluation of the central nervous system. Lifirafenib Vitamin E, specifically the isoform alpha-tocopherol (α-TP), is known to protect eNAD/EDM susceptible horses from developing the clinical phenotype. While vitamin E is an essential nutrient in the diet of horses, there are no diagnostic tests able to quantitate vitamin E and its metabolites in urine. An ultra-performance liquid chromatography-atmospheric-pressure chemical ionization mass spectrometry (UPLC-APCI-MS/MS) method was developed and validated following acidic hydrolysis and solid phase extraction to quantitate vitamin E and its metabolites in equine urine. A blank control horse urine matrix was used and spiked with different concentrations of analytes to form a standard curve using either alpha-tocopherol-d6 or chlorpropamide as the internal standard. Inter-day and intra-day statistics were performed to evaluate the method for accuracy (90% to 116%) and precision (0.75% to 14%). Matrix effects, percent recovery, and stability were also assessed. The method successfully analyzed alpha-carboxyethyl hydroxychroman (α-CEHC), alpha-carboxymethylbutyl hydroxychromans (α-CMBHC), gamma-carboxyethyl hydroxychroman γ-CEHC, and α-TP concentrations in urine to determine a baseline levels of analytes in healthy horses, and can be used to determine concentrations of vitamin E metabolites in equine urine allowing for its evaluation as a diagnostic approach in the treatment of eNAD/EDM.Patients with HPV-driven (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) have a significantly improved overall survival compared to patients with HPV-negative (HPV-) OPSCC. Nevertheless, 13%-25% of patients with HPV+OPSCC develop local/distant recurrence (LDR) and have a course of disease similar to HPV-OPSCC. We hypothesize that HPV+OPSCCs of patients with LDR have a mutation frequency and pattern similar to HPV-OPSCCs, which is associated with severe outcome. We performed targeted next-generation sequencing using a customized gene panel and compared data from 56 matched HPV+and HPV-OPSCC of patients with/without LDR regarding protein-altering variants. Despite improved overall survival of patients with HPV+OPSCC, those who develop LDR show a strongly reduced survival rate that is similar or even worse compared to HPV-OPSCC patients. Overall, the number of mutations was similar in OPSCC of patients with and without LDR. In total and with respect to TP53, HPV-OPSCC had significantly more protein-altering mutations than HPV+OPSCC. The number of mutations was similar in HPV-OPSCC of patients with and without LDR with the exception of FAT1, which was mutated more frequently in patients without LDR. In HPV+OPSCC, HRAS, PIK3R1, STK11 and TP63 were more frequently mutated in patients with LDR compared to patients without. HPV+OPSCC of patients with LDR have a similar mutation pattern as HPV-OPSCC, except TP53, which was mutated to a significantly lower extent. In conclusion, HPV-and HPV+OPSCC with LDR have similar mutation counts in the analyzed genes. We suspect that the number of mutations is not causal for disease progression, rather specific mutations could be important.