E2F7 upregulates MCM4 and fatty acid metabolism to advance lung adenocarcinoma metastasis

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators Pub Date : 2025-03-28 DOI:10.1016/j.prostaglandins.2025.106988

WuAsen Tang , Deming Zhang , Di Liu, Zikang Liu, Kuang Xiao, Chenggang Lei, Yalun Yang, Qian Zhou, Xianghui Wang

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引用次数: 0

Abstract

Background

MCM4, a key protein in MCM, is frequently overexpressed in cancers, but its specific role in lung adenocarcinoma (LUAD) metastasis is unclear.

Methods

Bioinformatics revealed the mRNA expression pattern of MCM4 in LUAD, which we confirmed in both normal lung epithelial and adenocarcinoma cell lines using qRT-PCR and western blot (WB). Cellular proliferation was gauged by cell counting kit-8 and colony formation assays, and the expression of epithelial-mesenchymal transition markers along with fatty acid synthase (FASN) was probed via WB. We employed Transwell to assess cellular migration and invasion, and utilized kits for quantifying intracellular triglycerides and phospholipids. Bioinformatics identified E2F7 as a potential transcriptional regulator of MCM4, prompting us to explore its relationship with MCM4, including predicted binding sites and E2F7 mRNA expression in LUAD. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to validate the regulatory effects of E2F7 on MCM4.

Results

MCM4 was found to be overexpressed in LUAD, and its knockdown inhibited cancer cell proliferation, migration, invasion, and metastasis, along with decreased FASN expression and declined levels of triglycerides and phospholipids within cells. Mechanistically, E2F7 transcriptionally activated MCM4, regulating fatty acid metabolism and promoting LUAD progression and metastasis.

Conclusion

Our study elucidates the mechanism by which E2F7 transcriptionally controls MCM4 to activate fatty acid metabolism, fueling LUAD metastasis. These discoveries emphasize the pivotal function of lipid metabolism in LUAD development and suggests new therapeutic targets for LUAD treatment.

查看原文本刊更多论文

E2F7上调MCM4和脂肪酸代谢，促进肺腺癌转移。

【背景】：MCM4是MCM的关键蛋白，在癌症中经常过表达，但其在肺腺癌（LUAD）转移中的具体作用尚不清楚。【方法】：生物信息学揭示了MCM4在LUAD中的mRNA表达模式，我们使用qRT-PCR和western blot （WB）技术在正常肺上皮细胞和腺癌细胞系中证实了这一表达模式。通过细胞计数试剂盒-8和集落形成试验检测细胞增殖，通过WB检测上皮-间质转化标记物和脂肪酸合成酶（FASN）的表达。我们使用Transwell评估细胞迁移和侵袭，并使用试剂盒定量细胞内甘油三酯和磷脂。生物信息学鉴定出E2F7是MCM4的潜在转录调节因子，促使我们探索其与MCM4的关系，包括预测的结合位点和E2F7 mRNA在LUAD中的表达。通过染色质免疫沉淀和双荧光素酶报告基因检测来验证E2F7对MCM4的调控作用。【结果】：在LUAD中发现MCM4过表达，其敲低抑制了癌细胞的增殖、迁移、侵袭和转移，同时FASN表达减少，细胞内甘油三酯和磷脂水平下降。机制上，E2F7转录激活MCM4，调节脂肪酸代谢，促进LUAD的进展和转移。【结论】本研究阐明了E2F7通过转录调控MCM4激活脂肪酸代谢，促进LUAD转移的机制。这些发现强调了脂质代谢在LUAD发展中的关键作用，并为LUAD治疗提供了新的治疗靶点。

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

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.