Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological...Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.展开更多
BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AG...BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AGI),but its specific mechanism is not completely understood,and few clinical reports are available.AIM To explore the effect and mechanism of HPA inhibition in S-AGI patients.METHODS In our prospective clinical trial,48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment,whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin.AGI grade,sequential organ failure assessment score,acute physiology and chronic health evaluation II score,D-dimer,activated partial thromboplastin time(APTT),anti-Xa factor,interleukin-6,tumour necrosis factor-α,HPA,syndecan-1(SDC-1),LC3B(autophagy marker),intestinal fatty acid binding protein,D-lactate,motilin,gastrin,CD4/CD8,length of intensive care unit(ICU)stay,length of hospital stay and 28-d survival on the 1^(st),3^(rd) and 7^(th) d after treatment were compared.Correlations between HPA and AGI grading as well as LC3B were compared.Receiver operator characteristic(ROC)curves were generated to evaluate the diagnostic value of HPA,intestinal fatty acid binding protein and D-lactate in S-AGI.RESULTS Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group(P<0.05).In addition,intestinal fatty acid-binding protein,D-lactate,AGI grade,motilin,and gastrin levels and sequential organ failure assessment score were significantly decreased(P<0.05)in the intervention group.However,LC3B,APTT,anti-Xa factor,and CD4/CD8 were significantly increased(P<0.05)in the intervention group.No significant differences in interleukin-6,tumour necrosis factor-α,d-dimer,acute physiology and chronic health evaluation II score,length of ICU stay,length of hospital stay,or 28-d survival were noted between the two groups(P>0.05).Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade.ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.CONCLUSION HPA has great potential as a diagnostic marker for S-AGI.Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms.The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.展开更多
目的探讨类肝素酶(heparanase,Hpa)与碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,TCCB)发生、发展中的作用及意义。方法应用免疫组织化学S-P法,检测69...目的探讨类肝素酶(heparanase,Hpa)与碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,TCCB)发生、发展中的作用及意义。方法应用免疫组织化学S-P法,检测69例BTCC和9例正常膀胱组织中Hpa和bFGF的表达。结果膀胱癌中,Hpa阳性表达率为42.03%;bFGF阳性表达率为44.93%;Hpa与bFGF共表达阳性率为31.89%;9例正常膀胱黏膜中均未见Hpa和bFGF阳性表达。Hpa与bFGF表达均随着膀胱癌病理分级和临床分期的升高而增强(P<0.05)。结论Hpa与bFGF可能作为预测膀胱移行细胞癌进展的指标及肿瘤治疗靶点,并有可能成为一个有效的预后指标。展开更多
AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori ...AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase(HPA) and mitogen-activated protein kinase(MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival(OS) and relapse-free survival(RFS) of GC patients were estimated by the KaplanMeier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC(70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK(P < 0.05); HPA expression was relevant to MAPK expression(P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing(P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases(P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.展开更多
Heparan sulphate proteoglycans (HSPGs) consist of a core protein and several heparan sulphate (HS) side chains covalently linked. HS also binds a great deal of growth factors, chemokines, cytokines and enzymes to the ...Heparan sulphate proteoglycans (HSPGs) consist of a core protein and several heparan sulphate (HS) side chains covalently linked. HS also binds a great deal of growth factors, chemokines, cytokines and enzymes to the extracellular matrix and cell surface. Heparanase can specially cleave HS side chains from HSPGs. There are a lot of conflicting reports about the role of heparanase in hepatocellular carcinoma (HCC). Heparanase is involved in hepatitis B virus infection and hepatitis C virus infection, the activation of signal pathways, metastasis and apoptosis of HCC. Heparanase is synthesized as an inactive precursor within late endosomes and lysosomes. Then heparanase undergoes proteolytic cleavage to form an active enzyme in lysosomes. Active heparanase translocates to the nucleus, cell surface or extracellular matrix. Different locations of heparanase may exert different activities on tumor progression. Furthermore, enzymatic activities and non-enzymatic activities of heparanase may play different roles during HCC development. The expression level of heparanase may also contribute to the discrepant effects of heparanase. Growth promoting as well as growth inhibiting sequences are contained within the tumor cell surface heparan sulfate. Degrading different HSPGs by heparanase may play different roles in HCC. Systemic studies examining the processing, expression, localization and function of heparanase should shed a light on the role of heparanase in HCC.展开更多
基金the Natural Science Foundation of Fujian Province(2021 J01539,2023 J011467)Scientific Foundation of the Fuzhou Health Commission(2021-S-wq21,2021-S-wp1).
文摘Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.
基金the Science and Technology Department of Gansu Province,No.20JR5RA35Science and Technology Project of Gansu Province,No.22JR10KA009+1 种基金Talent Innovation and Entrepreneurship Project of Science and Technology Bureau of Chengguan District,Lanzhou,No.2020RCCX0030Lanzhou Science and Technology Development Guiding Plan Project,No.2019-ZD-37.
文摘BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AGI),but its specific mechanism is not completely understood,and few clinical reports are available.AIM To explore the effect and mechanism of HPA inhibition in S-AGI patients.METHODS In our prospective clinical trial,48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment,whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin.AGI grade,sequential organ failure assessment score,acute physiology and chronic health evaluation II score,D-dimer,activated partial thromboplastin time(APTT),anti-Xa factor,interleukin-6,tumour necrosis factor-α,HPA,syndecan-1(SDC-1),LC3B(autophagy marker),intestinal fatty acid binding protein,D-lactate,motilin,gastrin,CD4/CD8,length of intensive care unit(ICU)stay,length of hospital stay and 28-d survival on the 1^(st),3^(rd) and 7^(th) d after treatment were compared.Correlations between HPA and AGI grading as well as LC3B were compared.Receiver operator characteristic(ROC)curves were generated to evaluate the diagnostic value of HPA,intestinal fatty acid binding protein and D-lactate in S-AGI.RESULTS Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group(P<0.05).In addition,intestinal fatty acid-binding protein,D-lactate,AGI grade,motilin,and gastrin levels and sequential organ failure assessment score were significantly decreased(P<0.05)in the intervention group.However,LC3B,APTT,anti-Xa factor,and CD4/CD8 were significantly increased(P<0.05)in the intervention group.No significant differences in interleukin-6,tumour necrosis factor-α,d-dimer,acute physiology and chronic health evaluation II score,length of ICU stay,length of hospital stay,or 28-d survival were noted between the two groups(P>0.05).Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade.ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.CONCLUSION HPA has great potential as a diagnostic marker for S-AGI.Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms.The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.
文摘目的探讨类肝素酶(heparanase,Hpa)与碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,TCCB)发生、发展中的作用及意义。方法应用免疫组织化学S-P法,检测69例BTCC和9例正常膀胱组织中Hpa和bFGF的表达。结果膀胱癌中,Hpa阳性表达率为42.03%;bFGF阳性表达率为44.93%;Hpa与bFGF共表达阳性率为31.89%;9例正常膀胱黏膜中均未见Hpa和bFGF阳性表达。Hpa与bFGF表达均随着膀胱癌病理分级和临床分期的升高而增强(P<0.05)。结论Hpa与bFGF可能作为预测膀胱移行细胞癌进展的指标及肿瘤治疗靶点,并有可能成为一个有效的预后指标。
基金Supported by the Natural Science Foundation of Gansu Province,No.1506RJZA255the National Natural Science Foundation of China,No.81572437+1 种基金the Open Topics of the Key Laboratory of Biological Treatment and Regenerative Medicine in Gansu Province,No.zdsyskfkt-201702the Fund of Donggang Branch,The First Hospital of Lanzhou University,No.ldyydgyn-201705
文摘AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase(HPA) and mitogen-activated protein kinase(MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival(OS) and relapse-free survival(RFS) of GC patients were estimated by the KaplanMeier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC(70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK(P < 0.05); HPA expression was relevant to MAPK expression(P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing(P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases(P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.
基金Supported by National Natural Science Foundation of China,No.30801495
文摘Heparan sulphate proteoglycans (HSPGs) consist of a core protein and several heparan sulphate (HS) side chains covalently linked. HS also binds a great deal of growth factors, chemokines, cytokines and enzymes to the extracellular matrix and cell surface. Heparanase can specially cleave HS side chains from HSPGs. There are a lot of conflicting reports about the role of heparanase in hepatocellular carcinoma (HCC). Heparanase is involved in hepatitis B virus infection and hepatitis C virus infection, the activation of signal pathways, metastasis and apoptosis of HCC. Heparanase is synthesized as an inactive precursor within late endosomes and lysosomes. Then heparanase undergoes proteolytic cleavage to form an active enzyme in lysosomes. Active heparanase translocates to the nucleus, cell surface or extracellular matrix. Different locations of heparanase may exert different activities on tumor progression. Furthermore, enzymatic activities and non-enzymatic activities of heparanase may play different roles during HCC development. The expression level of heparanase may also contribute to the discrepant effects of heparanase. Growth promoting as well as growth inhibiting sequences are contained within the tumor cell surface heparan sulfate. Degrading different HSPGs by heparanase may play different roles in HCC. Systemic studies examining the processing, expression, localization and function of heparanase should shed a light on the role of heparanase in HCC.
