ABSTRACT
BACKGROUND@#Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The ubiquitin-specific peptidase 25 (USP25) protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In this study, we aimed to investigate the function and mechanism of USP25 in the progression of HCC.@*METHODS@#We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database cohorts. Then, we constructed USP25-overexpressing and USP25-knockdown HepG2, MHCC97H, and L-O2 cells. We detected the biological function of USP25 by performing a series of assays, such as Cell Counting Kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway. The relationship between USP25 and tripartite motif-containing 21 (TRIM21) was assessed through mass spectrometry and co-immunoprecipitation (Co-IP) analysis. Finally, we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25.@*RESULTS@#USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to a poor prognosis. USP25 knockdown markedly reduced the proliferation, migration, and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition (EMT; E-cadherin, N-cadherin, and Snail) and the Wnt/β-catenin pathway (β-catenin, Adenomatous polyposis coli, Axin2 and Glycogen synthase kinase 3 beta) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo .@*CONCLUSIONS@#In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion, and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signaling pathway.
Subject(s)
Animals , Mice , beta Catenin/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , Ubiquitin Thiolesterase/metabolism , Wnt Signaling Pathway/geneticsABSTRACT
Sepsis is frequently associated with multi-system organ dysfunction and refractory hypotension,leading to a high mortality and poor prognosis.As an antioxidant,ascorbic acid (vitamin C) is an important auxiliary factor for many enzymes in the organism.Numerous studies have revealed that vitamin C can attenuate the inflammatory response,improve microcirculatory and hypotension in sepsis,and also can enhance the role of catecholamine in central nervous system,to prevent sepsis-induced organ failure and improve prognosis of patients.
ABSTRACT
[Abstract ] Objective Numerous studies had shown that synaptic-associated proteins (SNAPs) were closely related to the occurrence and development of tumors .The aim of this study was to investigate the expression of synaptosomal-associated protein 47 (SNAP47) and its correlation with the clinicopathological features in non-small cell lung cancer(NSCLC). Methods The expres-sions of SNAP family (SNAP23, SNAP25, SNAP29 and SNAP47) were extracted and analyzed through the gene expression microarray and the cancer genome atlas ( TCGA) data-base.SNAP47 mRNA expression in 52 cases of lung adenocarcinoma and their correspond-ing normal tissues were detected by quantitative real-time PCR ( qRT-PCR) . Results Among 52 cases of lung adenocarcinoma , SNAP47 mRNA expression levels of 41 cases(78.9%) were significantly higher than the adjacent lung tissue (P<0.05).The mRNA level of SNAP47 was associated with lymph node invasion and advanced clinical patho-logical stage .The mRNA levels of SNAP47 of patients in II/III stage were significantly higher than those of I stage patients ( 6.558 ± 4.730 vs 2.718 ±2.370, P<0.05).The mRNA levels of N1+N2 were higher than those of N0 (6.609 ±4.942 vs 3.360 ±2.987,P<0.05). Conclusion The high specificity of SNAP47 expression in lung cancer tissues might be associated with the invasion and lymph node metastasis of NSCLC , which is the potential therapeutic target of lung cancer .