SEC14L2 regulates the transport of cholesterol in non-small cell lung cancer through SCARB1.

IF 3.9 2区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Lipids in Health and Disease Pub Date : 2024-12-18 DOI:10.1186/s12944-024-02401-9
Qianhui Zhou, Dianwu Li, Yanchao Liang, Yunzhu Long, Yi Liu
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Abstract

Background: Inhibiting cholesterol metabolism has shown great potential in non-small cell lung cancer (NSCLC). However, the regulatory mechanism of the lipid metabolism key factor Sect. 14-like lipid binding 2 (SEC14L2) in NSCLC remains unclear. This study investigates the effects of differentially expressed genes related to cholesterol metabolism on the development of NSCLC.

Methods: Cox regression and survival analysis were performed to screen cholesterol metabolism-related genes and predict survival prognosis in NSCLC patients. The proliferation and migration of NSCLC cells were assessed by CCK-8, EdU, colony formation and wound-healing assay. Cholesterol depletion and rescue trials were used to evaluate the effect of SEC14L2 on cholesterol transport in NSCLC cells. IF and Co-IP were used to analyze the targeting relationship between SEC14L2 and scavenger receptor class B member 1 (SCARB1).

Results: SEC14L2 was a key gene related to prognosis in NSCLC patients and was highly expressed in A549 and Calu-1 cells. Subsequent studies demonstrated that knockdown of SEC14L2 significantly reduced the proliferation and migration of NSCLC cells, resulting in inhibited tumor growth. Furthermore, both in vitro and in vivo experiments indicated that SEC14L2 regulated cholesterol uptake. Silencing SEC14L2 partially counteracted the promotion of cholesterol content by MβCD-chol in A549 and Calu-1 cells. We then verified that there was a protein interaction between SEC14L2 and SCARB1.

Conclusion: SEC14L2 promoted cholesterol uptake in NSCLC cells by up-regulating SCARB1 expression, thereby promoting NSCLC development.

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SEC14L2通过SCARB1调控非小细胞肺癌中胆固醇的转运。
背景:抑制胆固醇代谢在非小细胞肺癌(NSCLC)中显示出巨大的潜力。然而,脂质代谢关键因子SEC14L2在NSCLC中的调控机制尚不清楚。本研究旨在探讨胆固醇代谢相关差异表达基因对非小细胞肺癌发展的影响。方法:采用Cox回归和生存分析,筛选非小细胞肺癌患者胆固醇代谢相关基因,预测生存预后。采用CCK-8、EdU、菌落形成和创面愈合试验评估非小细胞肺癌细胞的增殖和迁移。采用胆固醇消耗和挽救试验来评估SEC14L2对非小细胞肺癌细胞胆固醇转运的影响。使用IF和Co-IP分析SEC14L2与清道夫受体B类成员1 (SCARB1)的靶向关系。结果:SEC14L2是与NSCLC患者预后相关的关键基因,在A549和Calu-1细胞中高表达。随后的研究表明,敲低SEC14L2可显著降低NSCLC细胞的增殖和迁移,从而抑制肿瘤生长。此外,体外和体内实验均表明SEC14L2调节胆固醇摄取。沉默SEC14L2部分抵消了MβCD-chol对A549和Calu-1细胞中胆固醇含量的促进作用。然后我们验证了SEC14L2和SCARB1之间存在蛋白相互作用。结论:SEC14L2通过上调SCARB1表达促进NSCLC细胞胆固醇摄取,从而促进NSCLC的发展。
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来源期刊
Lipids in Health and Disease
Lipids in Health and Disease 生物-生化与分子生物学
CiteScore
7.70
自引率
2.20%
发文量
122
审稿时长
3-8 weeks
期刊介绍: Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.
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