Qianhui Zhou, Dianwu Li, Yanchao Liang, Yunzhu Long, Yi Liu
{"title":"SEC14L2 regulates the transport of cholesterol in non-small cell lung cancer through SCARB1.","authors":"Qianhui Zhou, Dianwu Li, Yanchao Liang, Yunzhu Long, Yi Liu","doi":"10.1186/s12944-024-02401-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>SEC14L2 promoted cholesterol uptake in NSCLC cells by up-regulating SCARB1 expression, thereby promoting NSCLC development.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"407"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653909/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lipids in Health and Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12944-024-02401-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.