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FUBP1 的过表达与人类宫颈癌的发生发展及预后相关。

Overexpression of FUBP1 is associated with human cervical carcinoma development and prognosis.

机构信息

Reproductive Medical Center, Guangzhou Women and Children's Medical Center of Sun Yat-sen University, Guangzhou, Guangdong, China.

Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.

出版信息

Life Sci. 2021 Mar 15;269:119098. doi: 10.1016/j.lfs.2021.119098. Epub 2021 Jan 18.

DOI:10.1016/j.lfs.2021.119098
PMID:33476628
Abstract

AIMS

Far upstream element-binding protein 1 (FUBP1) has been shown to involve in the tumorigenesis and tumor progression of various cancers. However, the expression and function of FUBP1 in cervical carcinoma remains unknown.

MAIN METHODS

Transcriptional expression of FUBP1 was initially evaluated using the Oncomine database, followed by evaluation of FUBP1 protein levels using immunohistochemistry in 119 cervical carcinoma patient tissues. In vitro experiments were performed to assess the tumorigenic role of FUBP1. Besides, Gene Set Enrichment Analysis, EnrichmentMap analysis, and protein-protein interaction (PPI) networks were used to evaluate the potential mechanisms of FUBP1 in promoting cervical cancer progression.

KEY FUNDINGS

In this research, we found both FUBP1 mRNA transcription and protein expression levels increased significantly in cervical carcinoma tissues compared with adjacent normal cervical tissues. Furthermore, elevated FUBP1 expression was positively correlated with age, T classification, N classification, tumor recurrence, Ki67 expression, and poor prognosis in cervical carcinoma patients. Besides, elevated FUBP1 expression acted as an independent unfavorable predictor for overall survival and disease-free survival in cervical carcinoma. Overexpression of FUBP1 significantly promoted cervical carcinoma cell proliferation and inhibits cell apoptosis in vitro, while knockdown of FUBP1 showed the opposite effect. Mechanistically, bioinformatics analysis revealed that FUBP1 promoted the biological function of cervical carcinoma cells via enhancing DNA repair signal pathways. Our results demonstrate for the first time that FUBP1 is a novel prognostic factor and therapeutic target for cervical carcinoma.

摘要

目的

远上游元件结合蛋白 1(FUBP1)已被证明参与多种癌症的发生和肿瘤进展。然而,FUBP1 在宫颈癌中的表达和功能尚不清楚。

主要方法

首先使用 Oncomine 数据库评估 FUBP1 的转录表达,然后使用免疫组织化学方法评估 119 例宫颈癌患者组织中的 FUBP1 蛋白水平。进行体外实验以评估 FUBP1 的致瘤作用。此外,还使用基因集富集分析、富集图分析和蛋白质-蛋白质相互作用(PPI)网络来评估 FUBP1 在促进宫颈癌进展中的潜在机制。

关键发现

在这项研究中,我们发现与相邻正常宫颈组织相比,宫颈癌组织中 FUBP1 的 mRNA 转录和蛋白表达水平均显著升高。此外,FUBP1 表达升高与宫颈癌患者的年龄、T 分类、N 分类、肿瘤复发、Ki67 表达和不良预后呈正相关。此外,FUBP1 表达升高是宫颈癌患者总生存和无病生存的独立不良预后因素。FUBP1 的过表达显著促进了宫颈癌细胞的体外增殖并抑制了细胞凋亡,而 FUBP1 的敲低则表现出相反的效果。通过生物信息学分析,我们发现 FUBP1 通过增强 DNA 修复信号通路来促进宫颈癌细胞的生物学功能。我们的研究结果首次表明,FUBP1 是宫颈癌的一个新的预后因素和治疗靶点。

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