Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inh...Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.展开更多
目的分析抑制素β-A(INHBA)在急性髓系白血病(AML)中的表达,并应用生物信息学技术探索及预测INHBA在AML中的生物学功能。方法收集2015年1月至2018年12月我院连续收治的AML患者骨髓标本120例及来源于造血干细胞移植供者的健康成人骨髓标...目的分析抑制素β-A(INHBA)在急性髓系白血病(AML)中的表达,并应用生物信息学技术探索及预测INHBA在AML中的生物学功能。方法收集2015年1月至2018年12月我院连续收治的AML患者骨髓标本120例及来源于造血干细胞移植供者的健康成人骨髓标本15例,采用细胞免疫组化、Western Blot、qRT-PCR等方法检测INHBA在AML不同细胞系及AML患者与正常成人中的表达水平;利用STRING数据库及KEGG富集分析构建INHBA蛋白质相互作用网络并预测其功能。结果INHBA在AML细胞系(Kasumi-1、KG-1及THP-1)中均有表达;qRT-PCR验证了INHBA在AML中的表达水平均值高于正常对照(0.718 vs 0.377),差异无统计学意义(P=0.286);蛋白质网络互作分析显示,与INHBA互作得分在0.90以上的17个蛋白,从高到低分别为FSTL3、ACVR2A、ACVR2B、ACVR1B、ACVR1C、ACVR1、ACVRL1、INHA、ENG、SMAD2、SMAD3、INHBB、SMAD4、IGSF1、FSHB、CGA、FKBP1A;KEGG富集分析显示,INHBA及其互作蛋白主要功能富集于TGF-β信号通路与BMP/Smad信号通路。结论INHBA在AML中高表达,可能通过调控TGF-β与BMP/Smad信号通路参与肿瘤的发生发展。展开更多
基金funded by Medical Science Foundation of Hebei University 2024B03Hebei Provincial Government-funded Provincial Medical Excellent Talent Project ZF2023025,ZF2024134,ZF2025045,ZF2025048,and ZF2025051+3 种基金Hebei Natural Science Foundation H2022206292,H2024206140Key R&D Program of Hebei Province 223777103D and 223777113DHebei Province County General Hospital Appropriate Health Technology Promotion Project 20220018other projects of Hebei Province SGH201501.
文摘Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.
文摘目的分析抑制素β-A(INHBA)在急性髓系白血病(AML)中的表达,并应用生物信息学技术探索及预测INHBA在AML中的生物学功能。方法收集2015年1月至2018年12月我院连续收治的AML患者骨髓标本120例及来源于造血干细胞移植供者的健康成人骨髓标本15例,采用细胞免疫组化、Western Blot、qRT-PCR等方法检测INHBA在AML不同细胞系及AML患者与正常成人中的表达水平;利用STRING数据库及KEGG富集分析构建INHBA蛋白质相互作用网络并预测其功能。结果INHBA在AML细胞系(Kasumi-1、KG-1及THP-1)中均有表达;qRT-PCR验证了INHBA在AML中的表达水平均值高于正常对照(0.718 vs 0.377),差异无统计学意义(P=0.286);蛋白质网络互作分析显示,与INHBA互作得分在0.90以上的17个蛋白,从高到低分别为FSTL3、ACVR2A、ACVR2B、ACVR1B、ACVR1C、ACVR1、ACVRL1、INHA、ENG、SMAD2、SMAD3、INHBB、SMAD4、IGSF1、FSHB、CGA、FKBP1A;KEGG富集分析显示,INHBA及其互作蛋白主要功能富集于TGF-β信号通路与BMP/Smad信号通路。结论INHBA在AML中高表达,可能通过调控TGF-β与BMP/Smad信号通路参与肿瘤的发生发展。
