ANGPT1 promotes M1 macrophage polarization and inhibits lung adenocarcinoma progression by inhibiting the TGF-β signalling pathway.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-03-01 DOI:10.4149/gpb_2024001

Gang Liu, Hao Zhang

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Abstract

Immune cells in the immune microenvironment of lung adenocarcinoma (LUAD) are involved in tumour progression. The aim of this study was to investigate the molecular mechanisms of immune infiltration-related genes in LUAD. The GEO, GeneCards, BioGPS and Genehopper databases were utilized to screen for immune infiltration-related differentially expressed genes (DEGs) in LUAD. Protein-protein interaction (PPI) network construction and survival analysis were performed in the Kaplan-Meier database to identify hub genes. The TIMER 2.0 database was used to analyse the correlations between hub gene expression and immune infiltration level. Co-culture of LUAD cells with macrophages and plasmid transfection to overexpress ANGPT1 were performed to investigate the function of the hub genes in LUAD using RT-qPCR, Western blot, CCK-8 assays, cell wound healing assays and transwell assays. A total of 88 immune infiltration-related DEGs were screened. The hub genes ANGPT1, CDH5 and CLDN5 were reduced in LUAD, while COL3A1 was overexpressed. ANGPT1 was significantly correlated with OS, FP and PPS, and ANGPT1 promoted the polarization of M1 macrophages. Further experiments revealed that ANGPT1 inhibited the proliferation, migration and invasion of LUAD cells by inhibiting the TGF-β signalling pathway. ANGPT1 promotes polarization of M1 macrophages and reduces the progression of LUAD by inhibiting the TGF-β signalling pathway. Thus, ANGPT1 could be employed as a predictive biomarker and immunotherapy target for lung cancer.

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ANGPT1 通过抑制 TGF-β 信号通路促进 M1 巨噬细胞极化并抑制肺腺癌的进展。

肺腺癌（LUAD）免疫微环境中的免疫细胞参与了肿瘤的进展。本研究旨在探讨肺腺癌中免疫浸润相关基因的分子机制。研究利用GEO、GeneCards、BioGPS和Genehopper数据库筛选LUAD中与免疫浸润相关的差异表达基因（DEGs）。在Kaplan-Meier数据库中构建了蛋白质-蛋白质相互作用（PPI）网络并进行了生存分析，以确定枢纽基因。TIMER 2.0数据库用于分析枢纽基因表达与免疫浸润水平之间的相关性。采用 RT-qPCR、Western 印迹、CCK-8 试验、细胞伤口愈合试验和透孔试验，将 LUAD 细胞与巨噬细胞共培养并转染质粒以过表达 ANGPT1，以研究 LUAD 中枢纽基因的功能。共筛选出 88 个与免疫浸润相关的 DEGs。中心基因ANGPT1、CDH5和CLDN5在LUAD中减少，而COL3A1则过表达。ANGPT1与OS、FP和PPS显著相关，ANGPT1促进了M1巨噬细胞的极化。进一步的实验发现，ANGPT1 通过抑制 TGF-β 信号通路，抑制了 LUAD 细胞的增殖、迁移和侵袭。ANGPT1 通过抑制 TGF-β 信号通路，促进了 M1 巨噬细胞的极化，并减少了 LUAD 的进展。因此，ANGPT1 可作为肺癌的预测性生物标志物和免疫治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.

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