海南医科大学学报2025，Vol.31Issue(5)：331-342,350,13.DOI:10.13210/j.cnki.jhmu.20241009.002
基于脂质组学探索LSD1抑制剂SP2509抗食管癌细胞增殖的分子机制
Lipidomics-based exploration of the molecular mechanism of LSD1 inhibitors against esophageal cancer cells proliferation
摘要
Abstract
Objective:Dysregulation of lipid metabolism is one of the most prominent metabolic characteristics of tumors.At present,the upstream regulatory mechanism of lipid metabolism in esophageal cancers(ESCA)remains unknown.Studies have shown that abnormal epigenetic modifications are most important factors leading to the dysregulation of lipid metabolism in tumors.Lysine-specific demethylase 1(LSD1),which mainly removes the methyl group from mono-and demethylated histone H3 at ly-sine 4 or lysine 9.However,it is still unclear whether LSD1 is related to lipid metabolism disorder in ESCA cells.Methods:We Used CCK8 cell proliferation assay,siRNA interference assay,Western blot assays,lipidomics technology and TCGA database to explore the mechanism by which LSD1 regulates the proliferation and lipid metabolism of ESCA cells.Results:There was obvi-ous lipid metabolism disorder in ESCA cells,which was manifested as significant upregulation of glycerophospholipids such as phosphatidylcholine(PC)and phosphatidylethanolamine(PE)and abnormal expression of related metabolic enzymes.LSD1 in-hibitor or LSD1 knockdown inhibited the proliferation of ESCA cells.LSD1 had a significant correlation with the expression of key enzymes which were involved in the synthesis and catabolism of phosphatidylcholine and phosphatidylethanolamine.Further,SP2509 treatment reduced the contents of PC and PE in cells,which also inhibited the activation of mTOR signaling pathway and down-regulated the expression of sterol regulatory element-binding factor 1(SREBF1).Conclusion:LSD1 is an upstream target involving in the regulation of glycerophospholipids metabolism in ESCA cells,and its mechanism may be related to the activation of mTOR pathway and the regulation of SREBF1 expression.This study reveals a novel role of LSD1 in the occurrence and devel-opment of tumors,and also provides a strong theoretical basis and potential therapeutic target for the development of precision treatment strategies for malignant tumors such as ESCA.关键词
脂质代谢失调/组蛋白赖氨酸去甲基化酶/食管癌/肿瘤细胞增殖/表观遗传修饰Key words
Dysregulation of lipid metabolism/Histone lysine demethylase/Esophageal carcinoma/Tumor cell prolifera-tion/Epigenetic modification分类
临床医学引用本文复制引用
李妍,杜原鑫,张俊飞,杨彩红,张雍偲,范彦英..基于脂质组学探索LSD1抑制剂SP2509抗食管癌细胞增殖的分子机制[J].海南医科大学学报,2025,31(5):331-342,350,13.基金项目
This study was supported by the National Natural Science Foundation of China(82304560) （82304560）
Natural Science Foundation of Shanxi Province(20210302124008) 国家自然科学基金资助项目(82304560) （20210302124008）
山西省自然科学基金资助项目(20210302124008) （20210302124008）
