Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 k...Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.展开更多
目的探讨Fox M1、Cep55及c-Myc蛋白在基底细胞样型乳腺癌(BLBC)中的表达及临床意义。方法采用免疫组化方法检测66例BLBC、70例NON-BLBC和66例癌旁正常乳腺组织中Fox M1、Cep55及c-Myc蛋白的表达情况及三者间的相互关系。结果 Fox M1蛋白...目的探讨Fox M1、Cep55及c-Myc蛋白在基底细胞样型乳腺癌(BLBC)中的表达及临床意义。方法采用免疫组化方法检测66例BLBC、70例NON-BLBC和66例癌旁正常乳腺组织中Fox M1、Cep55及c-Myc蛋白的表达情况及三者间的相互关系。结果 Fox M1蛋白在BLBC、NON-BLBC和癌旁正常乳腺组织中的阳性表达率分别为77.3%(51/66)、60.0%(42/70)、13.6%(9/66),Cep55蛋白在BLBC、NON-BLBC和癌旁正常乳腺组织中的阳性表达率分别为74.2%(49/66)、57.1%(40/70)、16.7%(11/66),c-Myc蛋白在BLBC、NON-BLBC和癌旁正常乳腺组织中的阳性表达率分别为71.2%(47/66)、54.3%(38/70)、22.7%(15/66),差异均有统计学意义(P<0.05)。Fox M1、Cep55及c-Myc蛋白的表达与BLBC的TNM分期及淋巴结转移情况密切相关(P<0.05),而与年龄、绝经与否、肿块大小无关(P>0.05)。Fox M1和Cep55蛋白在BLBC中的表达呈正相关关系(P<0.05),Fox M1和c-Myc蛋白在BLBC中的表达呈正相关关系(P<0.05),而Cep55与c-Myc的表达没有相关性(P>0.05)。结论 Fox M1、Cep55及c-Myc蛋白可能参与了BLBC的发生、发展,并且Fox M1分别与Cep55及c-Myc在BLBC发生发展过程中可能有一定的协同作用;Cep55蛋白与c-Myc蛋白在BLBC中的表达没有相关性,说明Cep55及c-Myc可能通过不同的作用对BLBC的发生发展过程产生影响。展开更多
目的分析中心体蛋白CEP55在肝癌中的表达情况及其与肝癌患者临床特征之间的潜在关系,预测CEP55在肝癌中的诊断及预后价值。方法从The Cancer Genome Atlas(TCGA)数据库下载肝癌的mRNA表达谱数据以及肝癌患者的临床特征数据。分析CEP55...目的分析中心体蛋白CEP55在肝癌中的表达情况及其与肝癌患者临床特征之间的潜在关系,预测CEP55在肝癌中的诊断及预后价值。方法从The Cancer Genome Atlas(TCGA)数据库下载肝癌的mRNA表达谱数据以及肝癌患者的临床特征数据。分析CEP55在正常肝组织和肝癌组织中的表达差异。利用Kruskal-Wallis检验、Wilcoxon signed-rank检验和逻辑回归的方法分析CEP55和临床特征之间的关系。采用Cox回归分析和Kaplan Meier方法分析CEP55对肝癌患者总生存期的影响。采用受试者工作特性曲线(ROC曲线)预测CEP55在肝细胞肿瘤中的诊断价值。利用Gene Set Enrichment Analysis(GSEA)对CEP55进行通路富集分析。结果与正常肝组织比较,CEP55在肝癌组织中明显高表达。CEP55与肝癌患者的年龄、临床分期、G分期、T分期具有显著的相关性,并与临床分期、G分期、T分期呈现出正相关。较高的CEP55表达量预示着肝癌患者具有较差的预后。多因素Cox回归分析结果提示CEP55是肝癌患者预后的独立危险因素。ROC曲线提示CEP55对于肝癌具有一定的诊断价值。GSEA通路富集分析提示CEP55与细胞周期、p53和mTOR信号通路、癌症通路、胰腺癌等具有相关性。结论CEP55在肝癌组织中明显高表达并与肝癌患者年龄、临床分期、G分期、T分期显著相关。CEP55可能是肝癌潜在的诊断和预后的标志物,其高表达预示着肝癌患者的预后较差。展开更多
Due to its difficulty in early diagnosis and lack of sensitivity to chemotherapy and radiotherapy,renal cell carcinoma(RCC)remains to be a frequent cause of cancer-related death.Here,we probed into new targets for its ...Due to its difficulty in early diagnosis and lack of sensitivity to chemotherapy and radiotherapy,renal cell carcinoma(RCC)remains to be a frequent cause of cancer-related death.Here,we probed into new targets for its early diagnosis and treatment for RCC.microRNA(miRNA)data of M2-EVs and RCC were searched on the Gene Expression Omnibus database,followed by the prediction of the potential downstream target.Expression of target genes was measured via RT-qPCR and Western blot,respectively.M2 macrophage was obtained viaflow cytometry with M2-EVs extracted.The binding ability of miR-342-3p to NEDD4L and to CEP55 ubiquitination was studied with their roles in the physical abilities of RCC cells assayed.Subcutaneous tumor-bearing mouse models and lung metastasis models were prepared to observe in vivo role of target genes.M2-EVs induced RCC growth and metastasis.miR-342-3p showed high expression in both M2-EVs and RCC cells.M2-EVs carrying miR-342-3p promoted RCC cell abilities to proliferate,invade and migrate.In RCC cells,M2-EV-derived miR-342-3p could specifically bind to NEDD4L and consequently elevate CEP55 protein expression via suppressing NEDD4L,thereby exerting tumor-promoting effects.CEP55 could be degraded by ubiquitination under the function of NEDD4L,and miR-342-3p delivered by M2-EVs facilitated the RCC occurrence and development by activating the PI3K/AKT/mTOR signaling pathway.In conclusion,M2-EVs promote RCC growth and metastasis by delivering miR-342-3p to suppress NEDD4L and subsequently inhibit CEP55 ubiquitination and degradation via activation of the PI3K/AKT/mTOR signaling pathway,strongly driving the proliferative,migratory and invasive of RCC cells.展开更多
目的:研究中心体相关蛋白55(centrosome associated protein 55,CEP55)在胆管癌组织和细胞中的表达情况,通过敲低CEP55研究其对胆管癌细胞增殖的影响。方法:通过RT-PCR、Western blot、免疫组化研究CEP55在胆管癌组织及细胞系中的表达情...目的:研究中心体相关蛋白55(centrosome associated protein 55,CEP55)在胆管癌组织和细胞中的表达情况,通过敲低CEP55研究其对胆管癌细胞增殖的影响。方法:通过RT-PCR、Western blot、免疫组化研究CEP55在胆管癌组织及细胞系中的表达情况,通过体外CCK8、平板克隆、EDU等功能实验研究敲低CEP55对胆管癌细胞增殖的影响。结果:CEP55在胆管癌组织和细胞系中均高表达,细胞功能实验显示敲低CEP55可降低胆管癌细胞的增殖能力,临床预后分析显示CEP55表达量高的患者预后较差。结论:CEP55在胆管癌组织和细胞中高表达,可促进胆管癌细胞的增殖能力,CEP55表达量高的患者预后较差。展开更多
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS)(2024-I2M-C&T-B-089)National Key Research and Development Program(2022YFC2504700,2022YFC2504701,2022YFC2504705)National Natural Science Foundation of China(NSFC81872216).
文摘Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.
文摘目的分析中心体蛋白CEP55在肝癌中的表达情况及其与肝癌患者临床特征之间的潜在关系,预测CEP55在肝癌中的诊断及预后价值。方法从The Cancer Genome Atlas(TCGA)数据库下载肝癌的mRNA表达谱数据以及肝癌患者的临床特征数据。分析CEP55在正常肝组织和肝癌组织中的表达差异。利用Kruskal-Wallis检验、Wilcoxon signed-rank检验和逻辑回归的方法分析CEP55和临床特征之间的关系。采用Cox回归分析和Kaplan Meier方法分析CEP55对肝癌患者总生存期的影响。采用受试者工作特性曲线(ROC曲线)预测CEP55在肝细胞肿瘤中的诊断价值。利用Gene Set Enrichment Analysis(GSEA)对CEP55进行通路富集分析。结果与正常肝组织比较,CEP55在肝癌组织中明显高表达。CEP55与肝癌患者的年龄、临床分期、G分期、T分期具有显著的相关性,并与临床分期、G分期、T分期呈现出正相关。较高的CEP55表达量预示着肝癌患者具有较差的预后。多因素Cox回归分析结果提示CEP55是肝癌患者预后的独立危险因素。ROC曲线提示CEP55对于肝癌具有一定的诊断价值。GSEA通路富集分析提示CEP55与细胞周期、p53和mTOR信号通路、癌症通路、胰腺癌等具有相关性。结论CEP55在肝癌组织中明显高表达并与肝癌患者年龄、临床分期、G分期、T分期显著相关。CEP55可能是肝癌潜在的诊断和预后的标志物,其高表达预示着肝癌患者的预后较差。
基金supported by the Science and Technology Department of Sichuan Province(2015SZ0117,2019YJ0701,and 2021YJ0239).
文摘Due to its difficulty in early diagnosis and lack of sensitivity to chemotherapy and radiotherapy,renal cell carcinoma(RCC)remains to be a frequent cause of cancer-related death.Here,we probed into new targets for its early diagnosis and treatment for RCC.microRNA(miRNA)data of M2-EVs and RCC were searched on the Gene Expression Omnibus database,followed by the prediction of the potential downstream target.Expression of target genes was measured via RT-qPCR and Western blot,respectively.M2 macrophage was obtained viaflow cytometry with M2-EVs extracted.The binding ability of miR-342-3p to NEDD4L and to CEP55 ubiquitination was studied with their roles in the physical abilities of RCC cells assayed.Subcutaneous tumor-bearing mouse models and lung metastasis models were prepared to observe in vivo role of target genes.M2-EVs induced RCC growth and metastasis.miR-342-3p showed high expression in both M2-EVs and RCC cells.M2-EVs carrying miR-342-3p promoted RCC cell abilities to proliferate,invade and migrate.In RCC cells,M2-EV-derived miR-342-3p could specifically bind to NEDD4L and consequently elevate CEP55 protein expression via suppressing NEDD4L,thereby exerting tumor-promoting effects.CEP55 could be degraded by ubiquitination under the function of NEDD4L,and miR-342-3p delivered by M2-EVs facilitated the RCC occurrence and development by activating the PI3K/AKT/mTOR signaling pathway.In conclusion,M2-EVs promote RCC growth and metastasis by delivering miR-342-3p to suppress NEDD4L and subsequently inhibit CEP55 ubiquitination and degradation via activation of the PI3K/AKT/mTOR signaling pathway,strongly driving the proliferative,migratory and invasive of RCC cells.
文摘目的:研究中心体相关蛋白55(centrosome associated protein 55,CEP55)在胆管癌组织和细胞中的表达情况,通过敲低CEP55研究其对胆管癌细胞增殖的影响。方法:通过RT-PCR、Western blot、免疫组化研究CEP55在胆管癌组织及细胞系中的表达情况,通过体外CCK8、平板克隆、EDU等功能实验研究敲低CEP55对胆管癌细胞增殖的影响。结果:CEP55在胆管癌组织和细胞系中均高表达,细胞功能实验显示敲低CEP55可降低胆管癌细胞的增殖能力,临床预后分析显示CEP55表达量高的患者预后较差。结论:CEP55在胆管癌组织和细胞中高表达,可促进胆管癌细胞的增殖能力,CEP55表达量高的患者预后较差。
