IGFBP1 promotes the proliferation and migration of lung adenocarcinoma cells through the PPARα pathway

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-08-20 DOI:10.1016/j.tranon.2024.102095

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引用次数: 0

Abstract

Background

The immune status is closely linked to cancer progression, metastasis, and prognosis. Lipid metabolism, crucial for reshaping immune status, plays a key role in regulating the advancement of lung adenocarcinoma (LUAD) and deserves further investigation.

Methods

This study classifies LUAD patients into different immune subtypes based on lipid metabolism-related genes and compares the clinical characteristics among these subtypes. Single-multi COX analysis screens out key genes related to prognosis, and a risk feature and prognostic model are constructed. Cell cloning, scratch, transwell, western blotting and flow cytometry cell cycle analysis to detect the function of key genes. A subcutaneous tumor animal model is used to investigate the in vivo function and molecular mechanisms of key genes.

Results

LUAD patients are classified into three immune subtypes, among which C3 subtype has lower immune status and higher frequency of gene mutations, and show lower immunoreactivity in immunotherapy. COX analysis identified a prognostic model for four lipid metabolism factors (IGFBP1, NR0B2, PPARA, and POMC). IGFBP1, a core gene in this model, is highly expressed in the C3 subtype. Functionally, knocking down IGFBP1 significantly inhibits tumor cell cloning, scratch, and migration abilities, and downregulates the expression of cell cycle and EMT-related proteins. Knocking down IGFBP1 significantly inhibits tumor burden (P < 0.05). Mechanistically, knocking down IGFBP1 inhibits the activation of PPARα to regulate tumor cell growth.

Conclusions

This study found that lipid metabolism genes are closely related to LUAD, and IGFBP1 may be a key gene in regulating tumor growth and development.

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IGFBP1 通过 PPARα 途径促进肺腺癌细胞的增殖和迁移

背景免疫状态与癌症的进展、转移和预后密切相关。本研究根据脂质代谢相关基因将肺腺癌患者分为不同的免疫亚型，并比较这些亚型的临床特征。单-多COX分析筛选出了与预后相关的关键基因，并构建了风险特征和预后模型。通过细胞克隆、划痕、跨孔、Western 印迹和流式细胞术细胞周期分析来检测关键基因的功能。结果LUAD患者被分为三种免疫亚型，其中C3亚型免疫状态较差，基因突变频率较高，在免疫治疗中表现出较低的免疫反应性。COX分析确定了四个脂质代谢因子（IGFBP1、NR0B2、PPARA和POMC）的预后模型。IGFBP1是该模型的核心基因，在C3亚型中高度表达。在功能上，敲除 IGFBP1 能显著抑制肿瘤细胞的克隆、划痕和迁移能力，并下调细胞周期和 EMT 相关蛋白的表达。敲除 IGFBP1 能明显抑制肿瘤负荷（P < 0.05）。结论本研究发现脂质代谢基因与LUAD密切相关，IGFBP1可能是调控肿瘤生长发育的关键基因。

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

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.