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技术文章

TROAP在STAT3的帮助下促进肾透明细胞癌的增殖、迁移和转移

点击次数:65 发布时间:2024/9/30 11:38:04

20236月,江南大学附属医院泌尿外科;南京医科大学附属医院泌尿外科;江南大学无锡医学院 (Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China;Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210008, China;Wuxi Medical College, Jiangnan University, Wuxi 214122, China) Jun Wang老师研究团队在International Journal of Molecular Sciences上发表论文:

TROAP Promotes the Proliferation, Migration, and Metastasis of Kidney Renal Clear Cell Carcinoma with the Help of STAT3”


TROAP在STAT3的帮助下促进肾透明细胞癌的增殖、迁移和转移”


Abstract

Kidney renal clear cell carcinoma (KIRC) is a subtype of renal cell carcinoma that threatens human health. The mechanism by which the trophinin-associated protein (TROAP)-an important oncogenic factor-functions in KIRC has not been studied. This study investigated the specific mechanism by which TROAP functions in KIRC. TROAP expression in KIRC was analyzed using the RNAseq dataset from the Cancer Genome Atlas (TCGA) online database. The Mann-Whitney U test was used to analyze the expression of this gene from clinical data. The Kaplan-Meier method was used for the survival analysis of KIRC. The expression level of TROAP mRNA in the cells was detected using qRT-PCR. The proliferation, migration, apoptosis, and cell cycle of KIRC were detected using Celigo, MTT, wound healing, cell invasion assay, and flow cytometry. A mouse subcutaneous xenograft experiment was designed to demonstrate the effect of TROAP expression on KIRC growth in vivo. To further investigate the regulatory mechanism of TROAP, we performed co-immunoprecipitation (CO-IP) and shotgun liquid chromatography-tandem mass spectrometry (LC-MS). TCGA-related bioinformatics analysis showed that TROAP was significantly overexpressed in KIRC tissues and was related to higher T and pathological stages, and a poor prognosis. The inhibition of TROAP expression significantly reduced the proliferation of KIRC, affected the cell cycle, promoted cell apoptosis, and reduced cell migration and invasion. The subcutaneous xenograft experiments showed that the size and weight of the tumors in mice were significantly reduced after TROAP-knockdown. CO-IP and post-mass spectrometry bioinformatics analyses revealed that TROAP may combine with signal transducer and activator of transcription 3 (STAT3) to achieve tumor progression in KIRC; this was verified by functional recovery experiments. TROAP may regulate KIRC proliferation, migration, and metastasis by binding to STAT3.

摘要:

肾透明细胞癌(KIRC)是一种严重威胁人类健康的肾细胞癌亚型。TROAP是一种重要的致癌因子,其在KIRC中的作用机制尚未得到研究。本研究探讨了TROAP在KIRC中的具体作用机制。使用来自癌症基因组图谱(TCGA)在线数据库的RNAseq数据集分析TROAP在KIRC中的表达。采用Mann-Whitney U检验从临床资料中分析该基因的表达。采用Kaplan-Meier法进行KIRC的生存分析。采用qRT-PCR检测细胞中TROAP mRNA的表达水平。采用Celigo、MTT、创面愈合、细胞侵袭试验和流式细胞术检测KIRC的增殖、迁移、凋亡和细胞周期。研究人员设计了小鼠皮下异种移植实验来证明TROAP表达对KIRC体内生长的影响。为了进一步研究TROAP的调控机制,研究人员采用了共免疫沉淀(CO-IP)和霰弹枪液相色谱-串联质谱(LC-MS)。tcga相关生物信息学分析显示,TROAP在KIRC组织中显著过表达,与高T及病理分期、预后差有关。抑制TROAP表达可显著降低KIRC的增殖,影响细胞周期,促进细胞凋亡,减少细胞迁移和侵袭。皮下异种移植实验表明,敲除troap后,小鼠肿瘤的大小和重量明显减小。CO-IP和质谱后生物信息学分析显示,TROAP可能与信号换能器和转录激活因子3 (STAT3)结合,在KIRC中实现肿瘤进展;功能恢复实验证实了这一点。TROAP可能通过结合STAT3调控KIRC的增殖、迁移和转移。


该论文中,KIRC细胞系786-O、ACHN和Caki-1的体外培养是使用Ausbian特级胎牛血清完成的欲了解或购Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.



原创作者:北京缔一生物科技有限公司

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