醛酮还原酶 1B10 通过调节整合素亚基α5 抑制胃癌细胞迁移、侵袭和黏附

Aldo-keto Reductase 1B10 Restrains Cell Migration, Invasion, and Adhesion of Gastric Cancer via Regulating Integrin Subunit Alpha 5.

机构信息

Department of Hepatobiliary - Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Division of General Surgery, Department of Gastrointestinal and Pancreatic Surgery, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.

Division of General Surgery, Department of Gastrointestinal and Pancreatic Surgery, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.

出版信息

Turk J Gastroenterol. 2023 Dec;34(12):1197-1205. doi: 10.5152/tjg.2023.22555.

DOI:10.5152/tjg.2023.22555

PMID:37823316

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10765221/

Abstract

BACKGROUND/AIMS: Gastric cancer is a prevalent malignancy with unfavorable prognosis partially resulting from its high metastasis rate. Clarifying the molecular mechanism of gastric cancer occurrence and progression for improvement of therapeutic efficacy and prognosis is needed. The study tended to delineate the role and regulatory mechanism of aldo-keto reductase 1B10 (AKR1B10) in gastric cancer progression.

MATERIALS AND METHODS

The relationship of AKR1B10 expression with survival rate in gastric cancer was analyzed through Kaplan-Meier analysis. The mRNA levels of AKR1B10 and integrin subunit alpha 5 (ITGA5) in gastric cancer tissues and cell lines were measured by real-time quantitative polymerase chain reaction. Protein levels of AKR1B10 and integrin subunit alpha 5 were assayed via western blot. The molecular relationship between AKR1B10 and ITGA5 was analyzed by co-immunoprecipitation assay. Cell viability was assayed through Cell Counting Kit-8, invasion and migration of tumor cells was assessed through wound healing and transwell assays. Transwell assay was utilized to detect invasion. The adhesion of gastric cancer cells was detected using cell adhesion assays.

RESULTS

The results unveiled that integrin subunit alpha 5 was upregulated, while AKR1B10 was downregulated in gastric cancer tissues and cells. Overexpressing AKR1B10 hindered gastric cancer cell proliferation, migration, invasion and adhesion. It was striking that we certified the inhibitory effect of AKR1B10 on integrin subunit alpha 5 expression and their (AKR1B10 and ITGA5)) negative relationship via bioinformatics method, real-time quantitative polymerase chain reaction, and co-immunoprecipitation assays. Via rescue experiments, it was concluded that AKR1B10 served as tumor suppressor potentially by ITGA5 expression in gastric cancer.

CONCLUSION

Our results indicated that AKR1B10 inhibited migration, invasion, and adhesion of gastric cancer cells via modulation of ITGA5.

摘要

背景/目的：胃癌是一种常见的恶性肿瘤，其预后不佳部分原因是其高转移率。阐明胃癌发生和发展的分子机制，对于提高治疗效果和预后是必要的。本研究旨在阐述醛酮还原酶 1B10（AKR1B10）在胃癌进展中的作用及其调控机制。

材料和方法

通过 Kaplan-Meier 分析分析 AKR1B10 表达与胃癌生存率的关系。采用实时定量聚合酶链反应检测胃癌组织和细胞系中 AKR1B10 和整合素亚基α5（ITGA5）的 mRNA 水平。通过 Western blot 检测 AKR1B10 和整合素亚基α5 的蛋白水平。通过共免疫沉淀分析检测 AKR1B10 和 ITGA5 之间的分子关系。通过细胞计数试剂盒-8 检测细胞活力，通过划痕愈合和 Transwell 测定评估肿瘤细胞的侵袭和迁移。Transwell 测定用于检测侵袭。用细胞黏附测定法检测胃癌细胞的黏附。

结果

结果表明，整合素亚基α5 在胃癌组织和细胞中上调，而 AKR1B10 下调。过表达 AKR1B10 抑制胃癌细胞增殖、迁移、侵袭和黏附。令人惊讶的是，我们通过生物信息学方法、实时定量聚合酶链反应和共免疫沉淀分析证实了 AKR1B10 对整合素亚基α5 表达的抑制作用及其（AKR1B10 和 ITGA5）的负相关关系。通过挽救实验得出结论，AKR1B10 通过调节 ITGA5 可能作为胃癌的肿瘤抑制因子。