ALB inhibits tumor cell proliferation and invasion by regulating immune microenvironment and endoplasmic reticulum stress in clear cell renal cell carcinoma

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-01 Epub Date: 2025-01-23 DOI:10.1016/j.bbadis.2025.167672

Jun-Ming Zhu , Shao-Hao Chen , Yi-Cheng Xu , Rui-Cheng Gao , Hai Cai , Qing-Shui Zheng , Xiong-Lin Sun , Xue-Yi Xue , Yong Wei , Ning Xu

{"title":"ALB inhibits tumor cell proliferation and invasion by regulating immune microenvironment and endoplasmic reticulum stress in clear cell renal cell carcinoma","authors":"Jun-Ming Zhu , Shao-Hao Chen , Yi-Cheng Xu , Rui-Cheng Gao , Hai Cai , Qing-Shui Zheng , Xiong-Lin Sun , Xue-Yi Xue , Yong Wei , Ning Xu","doi":"10.1016/j.bbadis.2025.167672","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this work is to identify putative hub genes for the advancement of clear cell renal cell carcinoma (ccRCC) and determine the fundamental mechanisms.</div></div><div><h3>Methods</h3><div>We employed multiple bioinformatics techniques to screen hub genes. Key hub gene expression levels in ccRCC were assessed. A plethora of functional experiments were carried out to explore the biological role of hub gene. Based on genome-wide association studies, a Mendelian randomization research was conducted to ascertain the causative relationship between albumin (ALB) and ccRCC.</div></div><div><h3>Results</h3><div>ALB was low expression in ccRCC tissues and cell lines. It was an independent predictor of progression-free survival following treatment and the overall survival of ccRCC patients. ALB overexpression exhibited the reverse effects of ALB knockdown, which increased cell proliferation, migration, and invasion while inhibiting cell death. Similarly, ALB overexpression inhibited the growth of ccRCC tumors in vivo. Consistent with functional enrichment analysis, ALB overexpression activates the endoplasmic reticulum stress (ERS) in vitro and vivo. The Mendelian randomization showed ALB was associated with the risk of ccRCC. Additionally, ALB was causally associated with γδT cells infiltrates in ccRCC.</div></div><div><h3>Conclusion</h3><div>ALB plays an important effect in ccRCC via activation of the ERS and regulating immune microenvironment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167672"},"PeriodicalIF":4.2000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular basis of disease","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0925443925000171","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

The aim of this work is to identify putative hub genes for the advancement of clear cell renal cell carcinoma (ccRCC) and determine the fundamental mechanisms.

Methods

We employed multiple bioinformatics techniques to screen hub genes. Key hub gene expression levels in ccRCC were assessed. A plethora of functional experiments were carried out to explore the biological role of hub gene. Based on genome-wide association studies, a Mendelian randomization research was conducted to ascertain the causative relationship between albumin (ALB) and ccRCC.

Results

ALB was low expression in ccRCC tissues and cell lines. It was an independent predictor of progression-free survival following treatment and the overall survival of ccRCC patients. ALB overexpression exhibited the reverse effects of ALB knockdown, which increased cell proliferation, migration, and invasion while inhibiting cell death. Similarly, ALB overexpression inhibited the growth of ccRCC tumors in vivo. Consistent with functional enrichment analysis, ALB overexpression activates the endoplasmic reticulum stress (ERS) in vitro and vivo. The Mendelian randomization showed ALB was associated with the risk of ccRCC. Additionally, ALB was causally associated with γδT cells infiltrates in ccRCC.

Conclusion

ALB plays an important effect in ccRCC via activation of the ERS and regulating immune microenvironment.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

ALB通过调节透明细胞肾细胞癌的免疫微环境和内质网应激抑制肿瘤细胞的增殖和侵袭。

目的：本研究旨在鉴定透明细胞肾细胞癌（ccRCC）进展的中心基因，并确定其基本机制。方法：采用多种生物信息学技术筛选枢纽基因。评估关键枢纽基因在ccRCC中的表达水平。为了探索枢纽基因的生物学作用，开展了大量的功能实验。在全基因组关联研究的基础上，进行孟德尔随机化研究，以确定白蛋白（ALB）与ccRCC之间的因果关系。结果：ALB在ccRCC组织和细胞系中低表达。它是ccRCC患者治疗后无进展生存期和总生存期的独立预测因子。ALB过表达表现出与ALB敲低相反的作用，它增加细胞的增殖、迁移和侵袭，同时抑制细胞死亡。同样，ALB过表达抑制体内ccRCC肿瘤的生长。与功能富集分析一致，ALB过表达在体外和体内激活内质网应激（ERS）。孟德尔随机化显示ALB与ccRCC的风险相关。此外，ALB与ccRCC中γδT细胞浸润有因果关系。结论：白蛋白通过激活内质网和调节免疫微环境在ccRCC中发挥重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.