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The incidence and mortality of hepatocellular carcinoma (HCC) is high, but the mechanisms underlying the growth and progression of HCC have not been elucidated. Recently, the ZIC family member 5 (ZIC5) is emerging as an oncogene in various types of tumors. However, its expression and biological role in HCC have not been reported. This study first demonstrated that ZIC5 was up-regulated in HCC specimens, and high ZIC5 expression indicated poor prognosis of HCC patients. In addition, over-expressed ZIC5 promoted the proliferation, migration and invasion of HCC cell lines Huh7 and HepG2 in vitro and in vivo , while ZIC5 knockdown achieved the opposite effects. Actually, ZIC5 increased the expression of genes participating in Wnt/β-catenin pathway such as β-catenin and CyclinD1. ZIC5 also promoted β-catenin to enter the nucleus of HCC cells. Furthermore, silencing β-catenin abated the promoting role of ZIC5 in HCC. Overall, this study reveals a novel mechanism of ZIC5/β-catenin that mediates the invasion and metastasis of HCC and ZIC5 serves as a novel indicator for prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

The epithelial-to-mesenchymal transition (EMT) induced by chronic hypoxia is one of the critical causes of renal fibrosis. Previous work reported that the transcription factors Twist plays an important role in hypoxia-induced EMT and renal fibrosis. Recent evidence indicates that miR-214 was regulated by Twist in many fibrotic diseases, but their role in hypoxia-induced EMT and renal fibrosis remains unknown. Here, we found that hypoxia significantly upregulated the expression of miR-214-3p in HK-2 cells, unilateral ureteral obstruction (UUO) nephropathy and patients with chronic kidney disease. Knockdown of miR-214-3p reversed the EMT of renal tubular epithelial cells (TECs) and alleviated fibrosis in the UUO mouse in vivo , while the overexpression of miR-214-3p promoted EMT phenotype and expression of fibrotic factors in TECs under hypoxic condition. In addition, Twist was also observed increased gradually with the prolongation of hypoxia, and it positively correlated with the expression of miR-214-3p in HK-2 cells transfected with Twist-overexpression or Twist-siRNA plasmid. Moreover, miR-214-3p negatively regulated the expression of epithelial cadherin (E-cadherin) by binding the E-cadherin 3′ UTR under hypoxic condition. Overall, hypoxia-induced activation of Twist/miR-214/E-cadherin axis is involved in the EMT of TECs, and anti-miR-214 may be an attractive strategy to ameliorate the progression of renal fibrosis. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is recognized as a serious global health problem due to its high prevalence and all-cause mortality. The aim of this research was to identify critical biomarkers and construct an integrated model for the early prediction of CKD. By using existing RNA-seq data and clinical information from CKD patients from the Gene Expression Omnibus (GEO) database, we applied a computational technique that combined the random forest (RF) and artificial neural network (ANN) approaches to identify gene biomarkers and construct an early diagnostic model. We generated ROC curves to compare the model with other markers and evaluated the associations of selected genes with various clinical properties of CKD. Moreover, we highlighted two biomarkers involved in energy metabolism pathways: pyruvate dehydrogenase kinase 4 (PDK4) and zinc finger protein 36 (ZFP36). The downregulation of the identified key genes was subsequently confirmed in both unilateral ureteral obstruction (UUO) and ischemia reperfusion injury (IRI) mouse models, accompanied by decreased energy metabolism. In vitro experiments and single-cell sequencing analysis proved that these key genes were related to the energy metabolism of proximal tubule cells and were involved in the development of CKD. Overall, we constructed a composite prediction model and discovered key genes that might be used as biomarkers and therapeutic targets for CKD. • An integrated predictive model for chronic kidney disease was constructed by machine learning. • PDK4 and ZFP36 were identified as biomarkers for predicting CKD. • PDK4 and ZFP36 were mainly expressed in proximal tubular cell and were downregulated in CKD. [ABSTRACT FROM AUTHOR]

Abstract Mucoepidermoid carcinoma (MEC) of salivary gland is a disease characterized by high rate of diatant metastasis, and associated with poor outcomes. However, the molecular mechanisms underlying the MEC remain poorly understand. Here, we simultaneously detected, for the first time, the expression profiles of mRNAs, lncRNAs, and circRNAs in four pairs of MEC and matched non-carcinoma tissues by microarrays. A total of 3612 mRNA, 3091 lncRNAs, and 284 circRNAs were altered during the pathogenesis of MEC. The functions of these differentially expressed RNAs were predicted by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were conducted to uncovered the hidden ceRNA mechanisms. Moreover, NONHSAT154433.1 that associated with ADAM12 and hsa_circ_0012342 were further screened and confirmed using qRT-PCR analysis. In conclusion, this study provides a systematic perspective on the potential function of non-coding RNAs (ncRNAs) in the molecular mechanisms of MEC. Among these, NONHSAT154433.1 and hsa_circ_0012342 might be served as potential prognostic biomarkers and therapeutic target of MEC. [ABSTRACT FROM AUTHOR]

Highlights: [•] GSNOR−/− mice are hypersensitive to pulmonary infection by Klebsiella pneumoniae. [•] Bacterial loads were increased over 4-folds in GSNOR−/− lung and 1000-folds in blood. [•] GSNOR−/− mice suffered significantly more inflammation and injury in spleen. [•] All wild-type mice survived the infection, but 40% of GSNOR−/− mice died. [ABSTRACT FROM AUTHOR]