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作者

Xingkai Li Hengchi Chen Lizhen Zhang Li Chen Wei Wei Shugeng Gao Qi Xue Yue Li Bing Wang Jiagen Li Yushun Gao Yanliang Lin

作者单位

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Xingkai Li, Hengchi Chen, Shugeng Gao, Qi Xue, Bing Wang, Jiagen Li & Yushun Gao <<#>> Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China Lizhen Zhang & Yanliang Lin <<#>> Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China Li Chen & Yanliang Lin <<#>> Shandong provincial Eco-environment Monitoring Center, Jinan, China Wei Wei <<#>> Department of Anesthesiology, Peking University Third Hospital, Beijing, China Yue Li

刊名

Oncogene

年份

2022

卷号

Vol.41 No.19

页码

2685-2695

ISSN

0950-9232

关键词

CANCER 25-HYDROXYCHOLESTEROL LIPIDS

摘要

Dietary cholesterol has been implicated to promote lung cancer. Lung adenocarcinoma is a main type of lung cancer, whereas the functional mechanism of cholesterol in LAC remained largely unknown. In the present study, we evidenced that cholesterol promoted cell proliferation and invasion of LAC in vitro as well as LAC metastasis in vivo. Cyp27A1 knockdown reduced the cholesterol-induced LAC cells proliferation and invasion. In contrast, Cyp7B1 knockdown enhanced the effect of cholesterol on LAC...更多

Dietary cholesterol has been implicated to promote lung cancer. Lung adenocarcinoma is a main type of lung cancer, whereas the functional mechanism of cholesterol in LAC remained largely unknown. In the present study, we evidenced that cholesterol promoted cell proliferation and invasion of LAC in vitro as well as LAC metastasis in vivo. Cyp27A1 knockdown reduced the cholesterol-induced LAC cells proliferation and invasion. In contrast, Cyp7B1 knockdown enhanced the effect of cholesterol on LAC cells proliferation and invasion. Furthermore, Cyp27A1 deficiency remarkably reduced high cholesterol-induced LAC metastasis in vivo. Mechanism investigation demonstrated that exposure of LAC cells to 27-hydroxycholesterol induced the phosphorylation of AKT and NFκB p65, and promoted the expression of peptidylprolyl isomerase B , especially in the coculture with THP1-derived macrophage. Meanwhile, 27-hydroxycholesterol induced the secretion of FGF2 and IL-6, which contributed to the expression of snail and vimentin. Luciferase report assay and ChIP assay confirmed that NFκB p65 controlled the transcription of PPIB. Inhibiting NFκB p65 activation reduced PPIB expression. PPIB inhibition reduced 27-hydroxycholesterol-induced expression of snail and vimentin. These results indicated that 27-hydroxycholesterol linked high cholesterol and LAC metastasis by regulating NFκB/PPIB axis and the secretion of FGF2 and IL-6.收起

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