Abstract
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.
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Abbreviations
- eQTL :
-
Expression quantitative trait locus
- GEO:
-
Gene Expression Omnibus
- LPC:
-
Lysophosphatidylcholine
- LPE:
-
Lysophosphatidylethanolamine
- PA:
-
Phosphatidic acid
- PC:
-
Phosphatidylcholine
- PE:
-
Phosphatidylethanolamine
- PG:
-
Phosphatidylglycerol
- PI:
-
Phosphatidylinositol
- PS:
-
Phosphatidylserine
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Funding
The work was supported by operation funding of the Shanghai Institute of Clinical Bioinformatics and Shanghai Engineering and Technology Center for Artificial Intelligence of Lung and Heart Diseases from Zhongshan Hospital, The National Nature Science Foundation of China (81873409), and National Key Research and Development Program of Precision Medicine (2017YFC0909500).
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Zhang, L., Lv, J., Chen, C. et al. 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 Biol Toxicol 37, 15–34 (2021). https://doi.org/10.1007/s10565-020-09520-w
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DOI: https://doi.org/10.1007/s10565-020-09520-w