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远上游元件结合蛋白1(FUBP1)是食管鳞状细胞癌(ESCC)中一种潜在的c-Myc调节因子,其表达促进ESCC进展。

Far upstream element-binding protein 1 (FUBP1) is a potential c-Myc regulator in esophageal squamous cell carcinoma (ESCC) and its expression promotes ESCC progression.

作者信息

Yang Lei, Zhu Jun-Ya, Zhang Jian-Guo, Bao Bo-Jun, Guan Cheng-Qi, Yang Xiao-Jing, Liu Yan-Hua, Huang Yue-Jiao, Ni Run-Zhou, Ji Li-Li

机构信息

Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.

Department of Gastroenterology, Affiliated Hospital of Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, China.

出版信息

Tumour Biol. 2016 Mar;37(3):4115-26. doi: 10.1007/s13277-015-4263-8. Epub 2015 Oct 21.

Abstract

The human far upstream element (FUSE) binding protein 1 (FUBP1) belongs to an ancient family which is required for proper regulation of the c-Myc proto-oncogene. Although c-Myc plays an important role in development of various carcinomas, the relevance of FUBP1 and their contribution to esophageal squamous cell carcinoma (ESCC) development remain unclear. In this study, we aimed to investigate the relationship between FUBP1 and c-Myc as well as their contribution to ESCC development. Western blot and immunohistochemical analyses were performed to evaluate FUBP1 expression. Coimmunoprecipitation analysis was performed to explore the correlation between FUBP1 and c-Myc in ESCC. In addition, the role of FUBP1 in ESCC proliferation was studied in ESCC cells through knocking FUBP1 down. The regulation of FUBP1 on proliferation was confirmed by Cell Counting Kit-8 (CCK-8) assay, flow cytometric assays, and clone formation assays. The expressions of FUBP1 and c-Myc were both upregulated in ESCC tissues. In addition to correlation between expression of FUBP1 and tumor grade, we also confirmed the correlation of FUBP1, c-Myc, and Ki-67 expression by twos. Moreover, upregulation of FUBP1 and c-Myc in ESCC was associated with poor survival. FUBP1 was confirmed to activate c-Myc in ESCC tissues and cells. FUBP1 was demonstrated to promote proliferation of ESCC cells. Moreover, downregulation of both FUBP1 and c-Myc was confirmed to inhibit proliferation of ESCC cells. Our results indicated that FUBP1 may potentially stimulate c-Myc expression in ESCC and its expression may promote ESCC progression.

摘要

人类远上游元件(FUSE)结合蛋白1(FUBP1)属于一个古老的家族,该家族对于原癌基因c-Myc的正常调控是必需的。尽管c-Myc在各种癌症的发生发展中起着重要作用,但FUBP1的相关性及其对食管鳞状细胞癌(ESCC)发生发展的贡献仍不清楚。在本研究中,我们旨在探讨FUBP1与c-Myc之间的关系及其对ESCC发生发展的贡献。进行蛋白质免疫印迹和免疫组织化学分析以评估FUBP1表达。进行免疫共沉淀分析以探讨ESCC中FUBP1与c-Myc之间的相关性。此外,通过敲低FUBP1在ESCC细胞中研究FUBP1在ESCC增殖中的作用。通过细胞计数试剂盒-8(CCK-8)测定、流式细胞术测定和克隆形成测定证实了FUBP1对增殖的调节作用。FUBP1和c-Myc在ESCC组织中的表达均上调。除了FUBP1表达与肿瘤分级之间的相关性外,我们还两两证实了FUBP1、c-Myc和Ki-67表达之间的相关性。此外,ESCC中FUBP1和c-Myc的上调与不良生存相关。证实FUBP1在ESCC组织和细胞中激活c-Myc。证明FUBP1促进ESCC细胞的增殖。此外,证实FUBPⅠ和c-Myc的下调均抑制ESCC细胞的增殖。我们的结果表明,FUBP1可能在ESCC中潜在地刺激c-Myc表达,其表达可能促进ESCC进展。

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