[Sphingomyelin phosphodiesterase 1 knockdown promotes exogenous dihomo-γ-linolenic acid-induced ferroptosis in acute myeloid leukemia cells].
Year: 2026
Type: article
Abstract: OBJECTIVES: To identify the potential target genes involved in the regulation of dihomo‑γ‑linolenic acid (DGLA)-induced ferroptosis in acute myeloid leukemia (AML) cells and to investigate their functional role in this process.. METHODS: . RESULTS: In the tumor-bearing mice, DGLA treatment markedly reduced the tumor volume and weight, and the tumor cells showed typical ultrastructural changes of ferroptosis with upregulated levels of ROS, MDA, and Fe²⁺ and increased mRNA and protein expression levels of TfR1 and PTGS2. RNA-seq combined with the FerrDb database analysis revealed significant upregulation of SMPD1 in AML cells with DGLA-induced ferroptosis. In THP-1 cells with SMPD1 knockdown, DGLA treatment significantly reduced the cell viability, aggravated mitochondrial ferroptotic injury, and increased intracellular ROS, MDA and Fe²⁺ levels, causing also significant reductions of protein levels of GPX4 and SLC7A11. In the mouse models bearing xenografts derived from THP-1 cells with SMPD1 knockdown, DGLA treatment significantly decreased tumor volume and weight and increased the expressions of the lipid peroxidation markers (MDA, ROS, and Fe²⁺) and the protein levels of TfR1 and PTGS2. CONCLUSIONS: .
Source: PubMed
Institution: Fujian Medical University
Language: Chinese
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223847565