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Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis

文献类型：期刊论文

作者Zhang, Rong2,3; Zhang, Zijia2,3; Wu, Wenyong1,2,3; Shi, Jingying2,3; Berk, Entezar2,3,4; Li, Wei2,3; Deng, Yanping2,3; Wang, Zhaojun2,3; Hou, Jinjun2,3; Long, Huali2,3
刊名METABOLOMICS
出版日期2023-01-16
卷号19期号:2页码:13
关键词Bufadienolides Prostate cancer Lipidomics Transcriptomics ELOVL6 PLD1
ISSN号1573-3882
DOI10.1007/s11306-022-01968-7
通讯作者Lei, Min(mlei@simm.ac.cn) ; Wu, Wanying(wanyingwu@simm.ac.cn)
英文摘要IntroductionLipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated.ObjectivesOur study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3).MethodsUntargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting.ResultsLipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect.ConclusionsAll these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.
WOS关键词TANDEM MASS-SPECTROMETRY ; CANCER ; GLYCEROPHOSPHOLIPIDS ; IDENTIFICATION ; PROLIFERATION ; SPHINGOMYELIN ; EXPRESSION ; DATABASE
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:000913643500001
出版者SPRINGER
源URL[http://119.78.100.183/handle/2S10ELR8/303699]  
专题中国科学院上海药物研究所
通讯作者Lei, Min; Wu, Wanying
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210029, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Natl Engn Ctr TCM Standardizat Technol, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Capital Med Univ, Sch Tradit Chinese Med, Beijing Key Lab TCM Collateral Dis Theory Res, Beijing 100069, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Rong,Zhang, Zijia,Wu, Wenyong,et al. Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis[J]. METABOLOMICS,2023,19(2):13.
APA Zhang, Rong.,Zhang, Zijia.,Wu, Wenyong.,Shi, Jingying.,Berk, Entezar.,...&Wu, Wanying.(2023).Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis.METABOLOMICS,19(2),13.
MLA Zhang, Rong,et al."Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis".METABOLOMICS 19.2(2023):13.

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来源：上海药物研究所

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