Yip1结构域家族成员4通过IER3IP1促进肝细胞癌的恶性进展OA
YIPF4 promotes the malignant progression of hepatocellular carcinoma via IER3IP1
目的 探讨Yip1结构域家族成员4(Yip1 domain family member 4,YIPF4)在肝细胞癌(hepatocellular carci-noma,HCC)恶性进展中的作用及机制.方法 分别使用生物信息学分析、Western blot及免疫组化检测YIPF4在HCC和癌旁非肿瘤肝组织中的表达水平及其与患者临床病理特征的关系;构建稳定敲低YIPF4表达的Hep3B和PLC/PRF/5细胞系进行体外实验,通过CCK-8、克隆形成和Transwell实验研究YIPF4对HCC细胞的增殖、迁移和侵袭能力的影响;cBioPortal数据库和GEPIA2数据库筛选出与其正相关的基因,即IER3相互作用蛋白1(immediate early response 3 interacting protein 1,IER3IP1),采用生物信息学与免疫组化法,检测IER3IP1在HCC与癌旁组织中的表达差异,并分析其与患者临床病理特征及YIPF4的相关性;最后,通过Western blot检测敲低YIPF4后IER3IP1的蛋白表达变化.结果 生物信息学分析和免疫组化结果显示,YIPF4在HCC组织中的表达高于癌旁非肿瘤肝组织(P均<0.05),IER3IP1在HCC组织中的表达高于癌旁非肿瘤肝组织(P均<0.05),YIPF4和IER3IP1在HCC中表达呈正相关(P<0.01);YIPF4高表达和IER3IP1高表达均与HCC患者的年龄、性别、HBV感染状态、是否有肝硬化以及血清AFP水平不显著相关(P均>0.05);YIPF4高表达和IER3IP1高表达均与HCC患者肿瘤大小和TNM分期显著相关(P均<0.05);CCK-8实验、克隆形成实验和Transwell实验结果显示,敲低YIPF4可抑制肝癌细胞的增殖、迁移和侵袭能力(P均<0.01);Western blot结果显示,敲低YIPF4后IER3IP1表达下调.结论 YIPF4在HCC中高表达,可能通过IER3IP1促进HCC的恶性进展,与病情进展密切相关,并且能够促进HCC的多种恶性表型和生物学行为,可能是HCC诊断和治疗的潜在生物学靶点.
Objective To investigate the role of Yip1 domain family member 4(YIPF4)in the malignant pro-gression of hepatocellular carcinoma(HCC).Methods Bioinformatics analysis,Western blot,and immunohisto-chemistry(IHC)were used to assess YIPF4 expression in HCC and adjacent non-tumor liver tissues and its association with clinicopathologic parameters.Stable YIPF4-knockdown Hep3B and PLC/PRF/5 cell lines were generated and sub-jected to CCK-8,colony formation,and Transwell assays to evaluate the effects of YIPF4 depletion on HCC cell prolif-eration,migration,and invasion.The cBioPortal and GEPIA2 databases were interrogated to identify genes positively correlated with YIPF4,revealing immediate early response 3 interacting protein 1(IER3IP1).The expression differ-ences of IER3IP1 in HCC and adjacent tissues were detected by bioinformatics and immunohistochemistry methods,and its correlations with the clinicopathological characteristics of patients and YIPF4 were analyzed,and Western blot was used to determine changes in IER3IP1 protein levels following YIPF4 knockdown.Results Both bioinformatic and IHC analyses demonstrated that YIPF4 and IER3IP1 were significantly upregulated in HCC tissues compared with adjacent non-tumor liver tissues(all P<0.05),and their expression levels were positively correlated(P<0.01).High YIPF4 and IER3IP1 expression showed no significant association with patient age,sex,HBV infection status,presence of cirrhosis,or serum AFP levels(all P>0.05),but correlated significantly with larger tumor size and ad-vanced TNM stage(all P<0.05).Functional assays revealed that YIPF4 knockdown markedly inhibited prolifera-tion,colony formation,migration,and invasion of HCC cells(all P<0.01).Western blot confirmed that IER3IP1 protein levels decreased following YIPF4 depletion.Conclusion YIPF4 is overexpressed in HCC and may drive ma-lignant progression by upregulating IER3IP1.Its expression correlates with aggressive clinicopathologic features and key malignant phenotypes in vitro,indicating that YIPF4-IER3IP1 axis could serve as a potential diagnostic and thera-peutic target in hepatocellular carcinoma.
王小嫣;卫晶晶;郭欠影;王晓楠;吴正升
安徽医科大学基础医学院 病理学教研室,合肥 230032安徽医科大学基础医学院 病理学教研室,合肥 230032安徽医科大学基础医学院 病理学教研室,合肥 230032安徽医科大学基础医学院 病理学教研室,合肥 230032安徽医科大学基础医学院 病原与免疫学实验室,合肥 230032
医药卫生
肝细胞癌YIPF4IER3IP1增殖迁移侵袭
hepatocellular carcinomaYIPF4IER3IP1proliferationmigrationinvasion
《临床与实验病理学杂志》 2026 (1)
20-29,10
国家自然科学基金项目(82103572) National Natural Science Foundation of China(82103572)
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