TFAP2A activates CTHRC1 to influence the migration of lung adenocarcinoma cells by modulating fatty acid metabolism

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators Pub Date : 2025-01-01 DOI:10.1016/j.prostaglandins.2024.106941

Xiaodong Zheng , Junzheng Zhou , Shiwei Nie , Yuan Chen , Xudong Wei , Jinrui Zhang , Xiaojuan Shen , Weimin Zhang

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引用次数: 0

Abstract

Background

Tumor metastasis is the main cause of death in lung adenocarcinoma (LAC) patients. It is known that the collagen triple helix repeats containing 1 (CTHRC1) protein is implicated in tissue remodeling and is tightly linked to the carcinogenesis and metastasis of solid tumors. However, the functional role of CTHRC1 and its potential mechanisms in LAC cell metastasis have not been fully explored.

Methods

The expression level of CTHRC1 in LAC was measured by using bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB). Small interfering RNA and overexpression methods were employed to investigate the function and molecular mechanisms of CTHRC1 in LAC cells. Through bioinformatics analysis, qRT-PCR, WB, scratch healing assay, Transwell, assay kits, and flow cytometry, the downstream pathways and upstream regulatory genes of CTHRC1 in LAC cells were investigated. The binding sites were verified by using chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene experiments.

Results

In this project, CTHRC1 was found to be abnormally upregulated in LAC tissues and cells. CTHRC1 promoted the migration and invasion of LAC cells. The promoting effect of CTHRC1 overexpression on LAC cell migration was weakened after the addition of orlistat (a fatty acid synthase inhibitor). Mechanistically, TF AP-2α (TFAP2A) was directly bound to the upstream sequence of the CTHRC1 promoter and promoted CTHRC1 expression. The TFAP2A-CTHRC1 axis induced the migration of LAC cells by activating fatty acid metabolism.

Conclusion

Our results indicated that TFAP2A activates fatty acid metabolism by positively modulating the expression of CTHRC1, thereby facilitating tumor cells’ migration and invasion. These findings provided novel insights into LAC treatment and future research.

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TFAP2A激活CTHRC1，通过调节脂肪酸代谢影响肺腺癌细胞的迁移。

背景：肿瘤转移是肺腺癌（LAC）患者死亡的主要原因。已知含有1 （CTHRC1）蛋白的胶原三螺旋重复序列与组织重塑有关，并与实体瘤的癌变和转移密切相关。然而，CTHRC1在LAC细胞转移中的功能作用及其潜在机制尚未被充分探讨。方法：采用实时荧光定量聚合酶链反应（qRT-PCR）和western blot技术结合生物信息学分析，检测CTHRC1在LAC中的表达水平。采用小干扰RNA和过表达方法研究CTHRC1在LAC细胞中的功能和分子机制。通过生物信息学分析、qRT-PCR、WB、划痕愈合实验、Transwell、检测试剂盒、流式细胞术等方法，研究CTHRC1在LAC细胞中的下游通路和上游调控基因。结合位点通过染色质免疫沉淀（ChIP）和双荧光素酶报告基因实验进行验证。结果：本项目发现CTHRC1在LAC组织和细胞中异常上调。CTHRC1促进LAC细胞的迁移和侵袭。添加奥利司他（脂肪酸合酶抑制剂）后，CTHRC1过表达对LAC细胞迁移的促进作用减弱。在机制上，TF AP-2α (TFAP2A)直接与CTHRC1启动子上游序列结合，促进CTHRC1表达。TFAP2A-CTHRC1轴通过激活脂肪酸代谢诱导LAC细胞迁移。结论：我们的研究结果表明，TFAP2A通过正向调节CTHRC1的表达来激活脂肪酸代谢，从而促进肿瘤细胞的迁移和侵袭。这些发现为LAC的治疗和未来的研究提供了新的见解。

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

Prostaglandins & other lipid mediators 生物-生化与分子生物学

CiteScore

5.80

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Prostaglandins & Other Lipid Mediators is the original and foremost journal dealing with prostaglandins and related lipid mediator substances. It includes basic and clinical studies related to the pharmacology, physiology, pathology and biochemistry of lipid mediators. Prostaglandins & Other Lipid Mediators invites reports of original research, mini-reviews, reviews, and methods articles in the basic and clinical aspects of all areas of lipid mediator research: cell biology, developmental biology, genetics, molecular biology, chemistry, biochemistry, physiology, pharmacology, endocrinology, biology, the medical sciences, and epidemiology. Prostaglandins & Other Lipid Mediators also accepts proposals for special issue topics. The Editors will make every effort to advise authors of the decision on the submitted manuscript within 3-4 weeks of receipt.