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Roles of acyl-CoA synthetase long-chain family member 5 and colony stimulating factor 2 in inhibition of palmitic or stearic acids in lung cancer cell proliferation and metabolism
Cell Biology and Toxicology ( IF 6.1 ) Pub Date : 2020-04-28 , DOI: 10.1007/s10565-020-09520-w
Linlin Zhang 1 , Jiapei Lv 2 , Chengshui Chen 1 , Xiangdong Wang 1, 2
Affiliation  

Lung cancer is a heterogeneous and complex disease with the highest incidence and mortality rate. The present study aims at defining the lung cancer phenome specificity of lipidomic profiles, screening target lipid-dependent transcriptional alternations, identifying target lipid-associated target genes, and exploring molecular mechanisms. Lung cancer-specific and lung cancer subtype-specific target lipids palmitic acid (C16:0) and stearic acid (C18:0) were found as target lipids by integrating clinical phenomics, lipidomics, and transcriptomics and exhibited antiproliferative effects in sensitive cells. The metabolism-associated gene ACSL5 or inflammation-associated gene CCL3 was identified in lung adenocarcinoma or small lung cancer cells, respectively. C16:0 or C18:0 could upregulate ACSL5 or CSF2 expression in a time- and dose-dependent pattern, and the deletion of both genes led to the insensitivity of cells. Target lipids increased the expression of PDK4 gene in different patterns and inhibited cell proliferation through alterations of intracellular energy. Thus, our data provide a new strategy to investigate the trans-points between clinical and phenomics and lipidomics and target lipid-associated molecular mechanisms to benefit from the discovery of new therapies.



中文翻译:

酰基辅酶A合成酶长链家族成员5和集落刺激因子2在抑制棕榈酸或硬脂酸在肺癌细胞增殖和代谢中的作用

肺癌是一种异质性和复杂的疾病,发病率和死亡率最高。本研究旨在确定脂质组谱的肺癌表型特异性,筛选靶脂依赖性转录改变,鉴定靶脂相关靶基因,探索分子机制。通过整合临床表型组学、脂质组学和转录组学,发现肺癌特异性和肺癌亚型特异性靶脂棕榈酸 (C16:0) 和硬脂酸 (C18:0) 作为靶脂,并在敏感细胞中表现出抗增殖作用。代谢相关基因 ACSL5 或炎症相关基因 CCL3 分别在肺腺癌细胞或小肺癌细胞中被发现。C16:0 或 C18:0 可以以时间和剂量依赖性模式上调 ACSL5 或 CSF2 的表达,两个基因的缺失导致细胞不敏感。目标脂质以不同的模式增加 PDK4 基因的表达,并通过改变细胞内能量来抑制细胞增殖。因此,我们的数据提供了一种新的策略来研究临床和表型组学和脂质组学之间的交叉点,并靶向脂质相关的分子机制,以从新疗法的发现中受益。

更新日期:2020-04-28
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