Open Access

Lipidomic profiling reveals lipid regulation by a novel LSD1 inhibitor treatment

  • Authors:
    • Yan Li
    • Xinying Qian
    • Yiyun Lin
    • Lei Tao
    • Zeping Zuo
    • Huaqin Zhang
    • Shengyong Yang
    • Xiaobo Cen
    • Yinglan Zhao
  • View Affiliations

  • Published online on: September 8, 2021     https://doi.org/10.3892/or.2021.8184
  • Article Number: 233
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lipid metabolic alterations are associated with cancer progression. Lysine‑specific demethylase 1 (LSD1) plays a crucial role in cancer and has become a promising target for cancer therapy. However, the effect of LSD1 on lipid metabolism remains unclear. In the present study, we used a LC‑MS/MS‑based lipidomics approach to investigate the impact of LSD1 on cancer cell lipid metabolism using ZY0511, a specific LSD1 inhibitor developed by our group as a specific probe. ZY0511 profoundly modified the human colorectal and cervical cancer cell lipid metabolism. A total of 256 differential metabolites were identified in HeLa cells, and 218 differential metabolites were identified in HCT116 cells, respectively. Among these lipid metabolites, phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine and sphingomyelin (SM) were downregulated by ZY0511. In contrast, ceramide (Cer) and a small portion of glycerophospholipids such as phosphatidylinositol and phosphatidylethanolamine were upregulated by ZY0511. These results revealed a disturbance in sphingolipids (SPs) and glycerophospholipids, which may be correlated with the progression of cancer. Furthermore, a marked increase in Cer and prominent decrease in SM were consistent with the upregulated expression of key enzymes in the Cer synthesis process including de novo synthesis, hydrolysis of SM and the salvage pathway after ZY0511 exposure. In conclusion, our research reveals a link between LSD1 and lipid metabolism in cancer cells, offering more comprehensive evidence for the application of LSD1 inhibitors for cancer therapy. The underlying mechanisms of how the LSD1 inhibitor regulates lipid metabolism warrant further investigation.
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November-2021
Volume 46 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Li Y, Qian X, Lin Y, Tao L, Zuo Z, Zhang H, Yang S, Cen X and Zhao Y: Lipidomic profiling reveals lipid regulation by a novel LSD1 inhibitor treatment. Oncol Rep 46: 233, 2021.
APA
Li, Y., Qian, X., Lin, Y., Tao, L., Zuo, Z., Zhang, H. ... Zhao, Y. (2021). Lipidomic profiling reveals lipid regulation by a novel LSD1 inhibitor treatment. Oncology Reports, 46, 233. https://doi.org/10.3892/or.2021.8184
MLA
Li, Y., Qian, X., Lin, Y., Tao, L., Zuo, Z., Zhang, H., Yang, S., Cen, X., Zhao, Y."Lipidomic profiling reveals lipid regulation by a novel LSD1 inhibitor treatment". Oncology Reports 46.5 (2021): 233.
Chicago
Li, Y., Qian, X., Lin, Y., Tao, L., Zuo, Z., Zhang, H., Yang, S., Cen, X., Zhao, Y."Lipidomic profiling reveals lipid regulation by a novel LSD1 inhibitor treatment". Oncology Reports 46, no. 5 (2021): 233. https://doi.org/10.3892/or.2021.8184