Epidemiology, molecular characterization, and drug resistance of IncHI5 plasmids from Enterobacteriaceae.

The increasingly frequent occurence of IncHI5 plasmids has attracted worldwide attention. The aim of this study was to perform an in-depth bioinformatics analysis to determine the genetic characteristics and global distribution of all IncHI5 plasmids. The geographic distribution and epidemiology of all IncHI5 plasmids from GenBank were analyzed based on relevant literature reports and background information from the National Center for Biotechnology Information (NCBI). Detailed annotation of antibiotic resistance genes was performed. A total of 65 IncHI5 plasmid genomes were collected in GenBank. All IncHI5 plasmids were carried by Enterobacteriaceae, of which Klebsiella pneumoniae accounted for the largest proportion (50%, 33/65). The host bacterium of IncHI5 plasmids was mainly isolated from Homo Sapiens (81%, 53/65). All strains carrying IncHI5 plasmids were mainly distributed in China (83%, 54/65). Evolutionary analysis can divide IncHI5 plasmids into two groups, namely Groups I/II, of which Group II was more widely distributed worldwide. This study showed that Enterobacteriaceae, especially Klebsiella, was the main host for IncHI5 plasmid. Almost all IncHI5 plasmids carried multiple types of antibiotic resistance genes, related to Tn1696 or Tn6535. The IncHI5 plasmids should be of continuing interest as good repositories for antibiotic resistance genes.

Interplay Between Long Noncoding RNA ZEB1-AS1 and miR-200s Regulates Osteosarcoma Cell Proliferation and Migration.

In our previous study, we found long noncoding RNA ZEB1-AS1 is upregulated and functions as an oncogene in osteosarcoma. MiR-200 family (miR-200s) functions as tumor suppressor via directly targeting ZEB1 in various cancers. In this study, we further investigate the potential interplay between ZEB1-AS1, miR-200s, and ZEB1 in osteosarcoma. Our results showed that ZEB1-AS1 functions as a molecular sponge for miR-200s and relieves the inhibition of ZEB1 caused by miR-200s. ZEB1-AS1 and miR-200s reciprocally negatively regulate each other. MiR-200s are downregulated in osteosarcoma tissues, and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in osteosarcoma. Functional experiments showed that consistent with ZEB1-AS1 depletion, miR-200s overexpression and ZEB1 depletion both inhibit osteosarcoma cell proliferation and migration. Overexpression of miR-200s partially abolished the effects of ZEB1-AS1 on osteosarcoma cell proliferation and migration. Moreover, the combination of ZEB1-AS1 depletion and miR-200s overexpression significantly inhibits osteosarcoma cell proliferation and migration. In conclusion, this study revealed a novel regulatory mechanism between ZEB1-AS1, miR-200s, and ZEB1. The interplay between ZEB1-AS1 and miR-200s contributes to osteosarcoma cell proliferation and migration, and targeting this interplay could be a promising strategy for osteosarcoma treatment. J. Cell. Biochem. 118: 2250-2260, 2017. © 2017 Wiley Periodicals, Inc.

Diagnostic and prognostic value of tissue and circulating levels of Ephrin-A2 in prostate cancer.

Ephrin-A2, a member of the Eph/ephrin family, is associated with tumorigenesis and tumor progression. This study aimed to assess the diagnostic and prognostic value of both serum and tissue levels of Ephrin-A2 in prostate cancer (PCa) management. One hundred and forty-five frozen prostate tissues, 55 paraffin-embedded prostate tissues, 88 serum samples, and seven prostate cell lines (RWPE-1, LNCaP, LNCaP-LN3, PC-3, PC-3M, PC-3M-LN4, and DU145) were examined via quantitative reverse transcription-PCR (qRT-PCR), immunohistochemistry, enzyme-linked immunosorbent assay, and western blotting. Induced Ephrin-A2 messenger RNA (mRNA) or protein expression was detected in 8.6 % (5/58) benign prostatic hyperplasia (BPH), 59.8 % (52/87) PCa, and five prostate cancer cell lines. Ephrin-A2 immunostaining was present in 6.7 % (1/15) patients with BPHs and 62.5 % (25/40) clinically localized PCa. Accordingly, serum Ephrin-A2 was significantly higher in PCa patients compared to those in the BPH patients and controls (P < 0.001). The expression of Ephrin-A2 was higher in tumor patients with an elevated Gleason score or T3-T4 staging. Ephrin-A2 expression was correlated with Ki-67 expression in PCa patients, both at the gene scale and protein level. Our data indicate that Ephrin-A2 is a potential diagnostic and prognostic biomarker and a promising molecular therapeutic target to attenuate prostate cancer progression.

Comprehensive Pan-Cancer Analysis Reveals the Role of UHRF1-Mediated DNA Methylation and Immune Infiltration in Renal Cell Carcinoma.

Ubiquitin-like PHD and ring finger domain protein 1 (UHRF1) are members of the multifunctional UHRF family, which can participate in DNA methylation change and histone posttranslational change through particular domains and participate in the event and development of tumors. The purpose of this study was to decide the molecular traits and potential medicine-based importance of UHRF1 that helped settle methylated immune infiltration in generalized cancer by carefully studying the relationship between UHRF1 expression and a variety of tumors and to further check for truth the functional role of UHRF1 in kidney-related cancer. A comprehensive analysis of UHRF1 in 33 cancers was performed based on TCGA database. This research involves analysis of mRNA expression profiles, prognostic value, immune infiltration, immune neoantigens, TMB, microsatellite instability, DNA methylation, and gene set enrichment analysis (GSEA). Both immune infiltration and DNA methylation were used to evaluate the importance and method of UHRF1 in renal cancer. The results showed that tumor tissue had higher expression level of UHRF1 than usual tissue. The high expression level of UHRF1 is related to the survival rate of renal cancer. UHRF1 expression was associated with tumor mutation load and microsatellite instability in different cancer types, and enrichment analysis identified terminology and pathways associated with UHRF1. This study showed that UHRF1 plays an important role in the group of objects and development of 33 tumors. UHRF1 may serve as a biomarker of immune infiltration and poor outlook of cancer.

Interfering with the Expression of Ubiquitin-Like with PHD and Ring Finger Domains 1 Can Inhibit the Invasion of Human Renal Cell Carcinoma.

Objective: The ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is a protein coding gene which is associated with colorectal cancer and other diseases. Therefore, the present study was aimed at investigating the effect and mechanism of UHRF1 protein on invasion and metastasis in human renal carcinoma cells. Methods: After UHRF1 was interfered with or overexpressed in renal carcinoma cell lines A498 and 769-P, the relative mRNA and protein level of UHRF1 was detected by RT-qPCR and immunofluorescence. The colony formation assay and MTT were performed to observe the proliferation and cell viability in each group. In addition, the invasion and metastasis of the cells in each group were detected by Transwell and wound healing assay. Finally, Western blot was utilized to measure protein expression of MMP-2 and MMP-9 and the level of protein in the Wnt/ß-catenin signaling pathway. Results: The cell ability, proliferation, invasion, and metastasis in A498 and 769-P cells were inhibited after interfering with UHRF1. In addition, the expression of MMP-2, MMP-9, c-myc, and ß-catenin was significantly decreased, while the expression of GSK-3ß was significantly increased. However, contrasting results were demonstrated when UHRF1 was overexpressed. Conclusions: Interference with the expression of UHRF1 was able to inhibit the invasion and metastasis of human renal carcinoma cell lines A498 and 769-P, which may be related to mediating the Wnt/ß-catenin signaling pathway and regulating the expression of MMP-2 and MMP-9.

Potential Key Markers for Predicting the Prognosis of Gastric Adenocarcinoma Based on the Expression of Ferroptosis-Related lncRNA.

Background: Gastric cancer is one of the most common malignant tumors, and it ranks third in global cancer-related mortality. This research was aimed at identifying new targeted treatments for gastric adenocarcinoma by constructing a ferroptosis-related lncRNA prognostic feature model. Methods: The gene expression profile and clinical data of gastric adenocarcinoma patients were downloaded from TCGA database. FerrDb database was used to determine the expression of iron death-related genes. We used R software to clean the TCAG gastric adenocarcinoma gene expression cohort and screen iron death-related differential genes and lncRNAs. The potential prognostic markers and immune infiltration characteristics were determined by constructing prognostic model and multivariate validation of lncRNA related to ferroptosis prognosis. Finally, the characteristics of immune infiltration were determined by immune correlation analysis. Results: We identified 26 ferroptosis-related lncRNAs with independent prognostic value. The Kaplan-Meier analysis identified high-risk lncRNAs associated with poor prognosis of STAD. The risk scoring model constructed by AC115619.1, AC005165.1, LINC01614, and AC002451.1 was better than traditional clinicopathological features. The 1-, 3-, and 5-year survival rates of STAD patients were predicted by the nomogram. GSEA reveals the oxidative respiration and tumor-related pathways in different risk groups. Immune analysis found significant differences in the expression of immune checkpoint-related genes TNFSF9, TNFSF4, and PDCD1LG2 between the two groups of patients. Meanwhile, there were significant differences in APC co stimulation, CCR, and checkpoint between the two groups. Conclusion: Based on the prognostic characteristics of ferroptosis-related lncRNAs, we identified the potential ferroptosis-related lncRNAs and immune infiltration characteristics in gastric adenocarcinoma, which will help provide new targeted treatments for gastric adenocarcinoma.