背景随着医医疗水平的提高,胃癌的早期诊断及治疗取得了明显成效,但患者的死亡率仍居高不下,且预后较差,侵袭与转移是影响患者预后的重要因素.因此,探究胃癌的发病机制,抑制胃癌细胞的侵袭转移,改善患者预后意义重大.乙酰肝素酶(heparan...背景随着医医疗水平的提高,胃癌的早期诊断及治疗取得了明显成效,但患者的死亡率仍居高不下,且预后较差,侵袭与转移是影响患者预后的重要因素.因此,探究胃癌的发病机制,抑制胃癌细胞的侵袭转移,改善患者预后意义重大.乙酰肝素酶(heparanase,HPSE)是一种内源性糖苷内切酶,有研究发现,期在胃癌组织中的表达水平明显升高.但关于乙酰肝素酶2(heparanase,HPSE2)在胃癌中的相关作用及其作用机制尚不明确.本研究旨在HPSE2在胃癌中的相关作用及其作用机制.目的分析HPSE2通过抑制核转录因子κB(NF-κB)、wnt基因/β-连环蛋白(Wnt/β-catenin)信号通路调控胃癌细胞恶性生物学行为的机制.方法收集2019-09/2021-04期间在本院进行手术切除治疗的74例胃癌患者的胃癌组织及癌旁正常组织,测定HPSE2的表达水平.将人胃癌细胞系MKN-28细胞进行传代培养并转染,获得HPSE2过表达组及对照组.测定各组细胞增殖能力、细胞凋亡率、细胞侵袭及迁移能力,并测定细胞中HPSE2、上皮型钙黏蛋白(epithelial cadherin,E-cadherin)、神经型钙黏蛋白(neuralcadherin,N-cadherin)、波形蛋白(Vimentin)、转化生长因子-β1(transforming growth factor-β1,T G F-β1)、磷酸化核转录因子-κBp65(n u c l e a r transcriptionfactorκBp65,p-NF-κBp65)、β-catenin表达水平变化.结果与癌旁正常组织对比,胃癌组织中HPSE2表达水平明显降低(P<0.01).与对照组比较,HPSE2过表达组HPSE2表达水平明显升高(P<0.01).两组1d时细胞增殖能力无明显差异(P>0.05);与2 d与对照组比较,H P S E2过表达组细胞增殖能力明显降低(P<0.05或P<0.01).与对照组比较,HPSE2过表达组细胞凋亡率及Bax、E-cadherin表达水平均明显升高,细胞侵袭、迁移能力及Bax、Suivivin、N-cadherin、Vimentin、TGF-β1、p-NF-κBp65、β-catenin表达水平均明显降低(P<0.01).结论上调HPSE2表达能够明显抑制细胞增殖、侵袭及迁移,抑制细胞发生EMT,促进细胞凋亡,其可能是通过抑制NF-κB及Wnt/β-catenin信号通路的激活实现.展开更多
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
文摘背景随着医医疗水平的提高,胃癌的早期诊断及治疗取得了明显成效,但患者的死亡率仍居高不下,且预后较差,侵袭与转移是影响患者预后的重要因素.因此,探究胃癌的发病机制,抑制胃癌细胞的侵袭转移,改善患者预后意义重大.乙酰肝素酶(heparanase,HPSE)是一种内源性糖苷内切酶,有研究发现,期在胃癌组织中的表达水平明显升高.但关于乙酰肝素酶2(heparanase,HPSE2)在胃癌中的相关作用及其作用机制尚不明确.本研究旨在HPSE2在胃癌中的相关作用及其作用机制.目的分析HPSE2通过抑制核转录因子κB(NF-κB)、wnt基因/β-连环蛋白(Wnt/β-catenin)信号通路调控胃癌细胞恶性生物学行为的机制.方法收集2019-09/2021-04期间在本院进行手术切除治疗的74例胃癌患者的胃癌组织及癌旁正常组织,测定HPSE2的表达水平.将人胃癌细胞系MKN-28细胞进行传代培养并转染,获得HPSE2过表达组及对照组.测定各组细胞增殖能力、细胞凋亡率、细胞侵袭及迁移能力,并测定细胞中HPSE2、上皮型钙黏蛋白(epithelial cadherin,E-cadherin)、神经型钙黏蛋白(neuralcadherin,N-cadherin)、波形蛋白(Vimentin)、转化生长因子-β1(transforming growth factor-β1,T G F-β1)、磷酸化核转录因子-κBp65(n u c l e a r transcriptionfactorκBp65,p-NF-κBp65)、β-catenin表达水平变化.结果与癌旁正常组织对比,胃癌组织中HPSE2表达水平明显降低(P<0.01).与对照组比较,HPSE2过表达组HPSE2表达水平明显升高(P<0.01).两组1d时细胞增殖能力无明显差异(P>0.05);与2 d与对照组比较,H P S E2过表达组细胞增殖能力明显降低(P<0.05或P<0.01).与对照组比较,HPSE2过表达组细胞凋亡率及Bax、E-cadherin表达水平均明显升高,细胞侵袭、迁移能力及Bax、Suivivin、N-cadherin、Vimentin、TGF-β1、p-NF-κBp65、β-catenin表达水平均明显降低(P<0.01).结论上调HPSE2表达能够明显抑制细胞增殖、侵袭及迁移,抑制细胞发生EMT,促进细胞凋亡,其可能是通过抑制NF-κB及Wnt/β-catenin信号通路的激活实现.
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.
