Objectives:KH-type splicing regulatory protein(KHSRP)is an RNA-binding protein involved in several cellular processes,including nuclear splicing,mRNA localization,and cytoplasmic degradation.While KHSRP’s role has be...Objectives:KH-type splicing regulatory protein(KHSRP)is an RNA-binding protein involved in several cellular processes,including nuclear splicing,mRNA localization,and cytoplasmic degradation.While KHSRP’s role has been studied in other cancers,its specific involvement in gastric cancer remains poorly understood.This study aims to explore KHSRP expression in gastric cancer and its potential effects on tumor progression and immune response.Methods:KHSRP expression in gastric cancer tissues and normal tissues was analyzed using data from The Cancer Genome Atlas(TCGA)database.The correlation between KHSRP expression,patient survival,and immune response was also assessed.Immunohistochemistry was performed to evaluate KHSRP expression in gastric cancer tissues.Gain-and loss-of-function experiments were conducted to assess KHSRP’s effects on gastric cancer cell proliferation,stemness,and migration.Furthermore,the impact of KHSRP silencing on tumor volume and immune cell infiltration was evaluated in a C3H/He mouse xenograft model.Results:KHSRP was found to be overexpressed in gastric cancer tissues compared to normal tissues,with a positive correlation to tumor stage and a negative correlation with patient prognosis.Functional assays revealed that KHSRP promotes gastric cancer cell proliferation,enhances cancer stem cell properties,and increases migratory capabilities in vitro.In vivo,KHSRP silencing led to a significant reduction in tumor volume and increased immune cell infiltration in the mouse xenograft model.Conclusions:KHSRP acts as an oncogene in gastric cancer by promoting tumorigenesis and suppressing anti-tumor immune responses.Its overexpression is associated with poor prognosis,making KHSRP a potential prognostic marker and therapeutic target in gastric cancer.展开更多
背景与目的:可变剪接在细胞增殖、生长、凋亡及分化等复杂的蛋白质功能调控中发挥着至关重要的作用,能参与包括肿瘤在内的多种疾病的发生、发展过程,目前大多数可变剪接调控因子的功能及其作用机制尚不清楚。本研究旨在探讨KH型剪接调...背景与目的:可变剪接在细胞增殖、生长、凋亡及分化等复杂的蛋白质功能调控中发挥着至关重要的作用,能参与包括肿瘤在内的多种疾病的发生、发展过程,目前大多数可变剪接调控因子的功能及其作用机制尚不清楚。本研究旨在探讨KH型剪接调控蛋白(KH-type splicing regulatory protein,KHSRP)在肺腺癌中的差异剪接靶基因及靶基因的表达与患者预后及免疫细胞功能的相关性。方法:通过高通量可变剪接测序,筛选KHSRP下游差异剪接靶基因。通过肿瘤免疫评估资源(Tumor IMmune Estimation Resource,TIMER)和阿拉巴马大学伯明翰分校癌症数据分析门户(the University of Alabama at Birmingham cancer data analysis portal,ULCAN)分析KHSRP下游差异剪接靶基因在肺腺癌中的表达。通过Kaplan数据库分析KHSRP下游差异剪接靶基因的表达与患者预后的相关性。通过TIMER免疫模块分析KHSRP下游差异剪接靶基因与免疫细胞功能的相关性。结果:NUMB、ADD3及LIMCH1为KHSRP的下游关键可变剪接靶基因。NUMB、ADD3及LIMCH1在肺腺癌肿瘤组织中均呈低表达,其低表达者预后不良。NUMB、ADD3及LIMCH1与免疫细胞功能呈正相关。结论:在肺腺癌中,NUMB、ADD3及LIMCH1为KHSRP的差异剪接靶基因,且NUMB、ADD3及LIMCH1低表达会导致预后不良,并且与免疫细胞功能呈正相关。展开更多
基金Supported by the Jiangxi Provincial Health Technology Project(No.202130037 to CWL)was also sponsored by the Jiangxi Provincial Health Technology Project(No.202410009 to SHL)。
文摘Objectives:KH-type splicing regulatory protein(KHSRP)is an RNA-binding protein involved in several cellular processes,including nuclear splicing,mRNA localization,and cytoplasmic degradation.While KHSRP’s role has been studied in other cancers,its specific involvement in gastric cancer remains poorly understood.This study aims to explore KHSRP expression in gastric cancer and its potential effects on tumor progression and immune response.Methods:KHSRP expression in gastric cancer tissues and normal tissues was analyzed using data from The Cancer Genome Atlas(TCGA)database.The correlation between KHSRP expression,patient survival,and immune response was also assessed.Immunohistochemistry was performed to evaluate KHSRP expression in gastric cancer tissues.Gain-and loss-of-function experiments were conducted to assess KHSRP’s effects on gastric cancer cell proliferation,stemness,and migration.Furthermore,the impact of KHSRP silencing on tumor volume and immune cell infiltration was evaluated in a C3H/He mouse xenograft model.Results:KHSRP was found to be overexpressed in gastric cancer tissues compared to normal tissues,with a positive correlation to tumor stage and a negative correlation with patient prognosis.Functional assays revealed that KHSRP promotes gastric cancer cell proliferation,enhances cancer stem cell properties,and increases migratory capabilities in vitro.In vivo,KHSRP silencing led to a significant reduction in tumor volume and increased immune cell infiltration in the mouse xenograft model.Conclusions:KHSRP acts as an oncogene in gastric cancer by promoting tumorigenesis and suppressing anti-tumor immune responses.Its overexpression is associated with poor prognosis,making KHSRP a potential prognostic marker and therapeutic target in gastric cancer.
文摘背景与目的:可变剪接在细胞增殖、生长、凋亡及分化等复杂的蛋白质功能调控中发挥着至关重要的作用,能参与包括肿瘤在内的多种疾病的发生、发展过程,目前大多数可变剪接调控因子的功能及其作用机制尚不清楚。本研究旨在探讨KH型剪接调控蛋白(KH-type splicing regulatory protein,KHSRP)在肺腺癌中的差异剪接靶基因及靶基因的表达与患者预后及免疫细胞功能的相关性。方法:通过高通量可变剪接测序,筛选KHSRP下游差异剪接靶基因。通过肿瘤免疫评估资源(Tumor IMmune Estimation Resource,TIMER)和阿拉巴马大学伯明翰分校癌症数据分析门户(the University of Alabama at Birmingham cancer data analysis portal,ULCAN)分析KHSRP下游差异剪接靶基因在肺腺癌中的表达。通过Kaplan数据库分析KHSRP下游差异剪接靶基因的表达与患者预后的相关性。通过TIMER免疫模块分析KHSRP下游差异剪接靶基因与免疫细胞功能的相关性。结果:NUMB、ADD3及LIMCH1为KHSRP的下游关键可变剪接靶基因。NUMB、ADD3及LIMCH1在肺腺癌肿瘤组织中均呈低表达,其低表达者预后不良。NUMB、ADD3及LIMCH1与免疫细胞功能呈正相关。结论:在肺腺癌中,NUMB、ADD3及LIMCH1为KHSRP的差异剪接靶基因,且NUMB、ADD3及LIMCH1低表达会导致预后不良,并且与免疫细胞功能呈正相关。
