Objective:Ring finger protein 145(RNF145),an E3 ubiquitin ligase,is significantly upregulated in hepatocellular carcinoma(HCC).However,its role in HCC remains unknown.The study aimed to investigate the functions and u...Objective:Ring finger protein 145(RNF145),an E3 ubiquitin ligase,is significantly upregulated in hepatocellular carcinoma(HCC).However,its role in HCC remains unknown.The study aimed to investigate the functions and underlying mechanisms of RNF145 in HCC.Methods:The role of RNF145 in HCC was investigated using data from The Cancer Genome Atlas(TCGA)and in vitro experimental assays.Its oncogenic functions were assessed using the transwell migration assay and the wound-healing assay.The molecular mechanism was explored through protein immunoprecipitation and western blot analyses.Data from public databases were analyzed to correlate RNF145 expression with clinicopathological features.Univariate and multivariate Cox analyses established RNF145 as an independent prognostic factor.Subsequently,a prognostic nomogram was constructed.Results:RNF145 was upregulated in HCC.The expression level of RNF145 in HCC showed significant correlations with histological grade,pathological stage,and vascular invasion.Functionally,knockdown of RNF145 effectively abolished the migratory and invasive capacities of HCC cells.This pro-metastatic effect is mediated through the RNF145-driven ubiquitination and subsequent degradation of protocadherin 9(PCDH9).Conclusion:Our findings confirm the significant upregulation of RNF145 in HCC and promote metastasis by facilitating PCDH9 ubiquitination and degradation,highlighting its role as a prognostic biomarker and a potential therapeutic target.展开更多
基金supported by Guangdong Basic and Applied Basic Research Foundation(2024A1515012800)Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province(CXPJJH125001-2540).
文摘Objective:Ring finger protein 145(RNF145),an E3 ubiquitin ligase,is significantly upregulated in hepatocellular carcinoma(HCC).However,its role in HCC remains unknown.The study aimed to investigate the functions and underlying mechanisms of RNF145 in HCC.Methods:The role of RNF145 in HCC was investigated using data from The Cancer Genome Atlas(TCGA)and in vitro experimental assays.Its oncogenic functions were assessed using the transwell migration assay and the wound-healing assay.The molecular mechanism was explored through protein immunoprecipitation and western blot analyses.Data from public databases were analyzed to correlate RNF145 expression with clinicopathological features.Univariate and multivariate Cox analyses established RNF145 as an independent prognostic factor.Subsequently,a prognostic nomogram was constructed.Results:RNF145 was upregulated in HCC.The expression level of RNF145 in HCC showed significant correlations with histological grade,pathological stage,and vascular invasion.Functionally,knockdown of RNF145 effectively abolished the migratory and invasive capacities of HCC cells.This pro-metastatic effect is mediated through the RNF145-driven ubiquitination and subsequent degradation of protocadherin 9(PCDH9).Conclusion:Our findings confirm the significant upregulation of RNF145 in HCC and promote metastasis by facilitating PCDH9 ubiquitination and degradation,highlighting its role as a prognostic biomarker and a potential therapeutic target.
文摘目的探究急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者外周血微小核糖核酸(microRNA,miRNA)-145-5p、miR-27b-3p浓度对经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后并发心力衰竭(heart failure,HF)的预测价值。方法选择于2021年1月至2023年2月于成都市第五人民医院就诊的STEMI患者176例(均行PCI治疗)作为观察对象,观察STEMI患者PCI治疗后HF的发生情况,分为发生组和未发生组。实时定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)法检测外周血miR-145-5p、miR-27b-3p浓度。Pearson法、Spearman法分析血清miR-145-5p、miR-27b-3p及二者与一般资料的相关性。STEMI患者发生HF的影响因素采用多因素Logistic回归分析。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清miR-145-5p、miR-27b-3p对STEMI患者PCI治疗后发生HF的预测价值。结果两组患者的病变支数、血清同型半胱氨酸(homocysteine,Hcy)、超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)浓度比较,差异有统计学意义(P<0.05)。发生组患者的血清miR-145-5p、miR-27b-3p浓度高于未发生组,差异有统计学意义(P<0.05)。根据Spearman相关性分析得知,血清miR-145-5p、miR-27b-3p浓度与病变支数呈正相关(P<0.05)。根据Pearson相关性分析得知,血清miR-145-5p浓度与miR-27b-3p浓度呈正相关(P<0.05);血清miR-145-5p、miR-27b-3p浓度与Hcy、hs-CRP浓度呈正相关(P<0.05)。多因素Logistic回归分析显示多支病变、Hcy、hs-CRP、miR-145-5p、miR-27b-3p为影响STEMI患者PCI治疗后发生HF的危险因素(P<0.05)。血清miR-145-5p预测STEMI患者PCI治疗后发生HF的曲线下面积(area under the curve,AUC)为0.896,血清miR-27b-3p预测STEMI患者PCI治疗后发生HF的AUC为0.883,二者联合预测STEMI患者发生HF的AUC为0.962,二者联合优于各自单独预测(P<0.05)。结论miR-145-5p、miR-27b-3p浓度升高与STEMI患者PCI治疗后发生HF相关,两者联合对STEMI患者PCI治疗后发生HF具有较高的预测价值。
