胃癌细胞中GRB7蛋白上调与临床特征相关,并增加细胞增殖和干细胞特性。

Up-regulated GRB7 protein in gastric cancer cells correlates with clinical properties and increases proliferation and stem cell properties.

作者信息

Pei Yuan-Yuan, Ran Jian, Wen Lijuan, Liu Xiaoyi, Xiang Li, Liu Weiqiang, Wei Fengxiang

机构信息

The Central Laboratory, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, China.

The Digestive Department, Longgang District People's Hospital of Shenzhen City, Shenzhen, China.

出版信息

Front Oncol. 2023 Jan 4;12:1054976. doi: 10.3389/fonc.2022.1054976. eCollection 2022.

Abstract

INTRODUCTION

It has been reported that GRB7 is closely related to a variety of human solid tumors, but its role in gastric cancer has not been reported yet. The purpose of this study was to investigate the expression level and intracellular effects of GRB7 in human gastric cancer.

METHODS

Real-time fluorescent quantitative PCR and Western blot were used to detect the expression of GRB7 in gastric cancer cell lines. The immunohistochemical staining and SPSS analysis verified the GRB7 protein expression. Stable gastric cancer cell lines, MTT experiments, clone formation experiments, cell cycle flow cytometry experiments, sphere formation experiments and lateral subpopulation cell sorting experiments were conducted to investigate the role of GRB7 in gastric cancer cells.

RESULTS

We found that the expression of GRB7 in gastric cancer cell lines was higher than that of the corresponding normal gastric epithelial cells, and correspondingly higher in gastric cancer tissues than its paired adjacent tissues. GRB7 protein was expressed more highly in cancer tissues than in adjacent tissues. GRB7 protein expression levels were positively correlated with the clinical stage of gastric cancer patients, and negatively correlated with the survival prognosis of patients. GSEA analysis of GRB7 mRNA levels in gastric cancer tissues and normal gastric epithelial tissues from public databases showed that GRB7 may affect cell proliferation and related processes of intracellular stem cells. GRB7 can promote the proliferation of gastric cancer cells and is positively related to the self-renewal ability of gastric cancer stem cells.

DISCUSSION

This study shows that GRB7 molecules highly expressed in gastric cancer tissues can promote the proliferation of gastric cancer cells and increase the proportion of gastric cancer stem cells, so it is expected to become a diagnostic molecule or potential therapeutic target for gastric cancer.

摘要

引言

据报道,GRB7与多种人类实体瘤密切相关,但其在胃癌中的作用尚未见报道。本研究旨在探讨GRB7在人类胃癌中的表达水平及细胞内效应。

方法

采用实时荧光定量PCR和蛋白质免疫印迹法检测GRB7在胃癌细胞系中的表达。免疫组织化学染色及SPSS分析验证GRB7蛋白表达。通过构建稳定的胃癌细胞系、MTT实验、克隆形成实验、细胞周期流式细胞术实验、成球实验及侧向亚群细胞分选实验,研究GRB7在胃癌细胞中的作用。

结果

我们发现,GRB7在胃癌细胞系中的表达高于相应的正常胃上皮细胞,在胃癌组织中的表达也相应高于其配对的癌旁组织。GRB7蛋白在癌组织中的表达高于癌旁组织。GRB7蛋白表达水平与胃癌患者的临床分期呈正相关,与患者的生存预后呈负相关。对公共数据库中胃癌组织和正常胃上皮组织的GRB7 mRNA水平进行基因集富集分析(GSEA)表明,GRB7可能影响细胞增殖及细胞内干细胞的相关过程。GRB7可促进胃癌细胞增殖,且与胃癌干细胞的自我更新能力呈正相关。

讨论

本研究表明,在胃癌组织中高表达的GRB7分子可促进胃癌细胞增殖并增加胃癌干细胞比例,因此有望成为胃癌的诊断分子或潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56d1/9846623/70cc5160ec60/fonc-12-1054976-g001.jpg

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