Aberrant lipid metabolism is a hallmark of malignant cancers. Recent studies have shown that abnormal activation of the lipolysis pathway might contribute to acute myeloid leukemia (AML) progression. However, the molecular mechanism through which lipid metabolism mediates AML progression is unknown. RNA-sequencing was used to screen out the target gene pnpla2/ATGL(adipose triglyceride lipase), which showed differential expression in AML. A comparison was made of ATGL mRNA levels in different AML cell lines by real-time PCR. ATGL expression was blocked using siRNAs, and then ATGL expression, proliferation, apoptosis, and cell cycle progression of si-ATGL AML cell lines and si-control AML cell lines were respectively tested. Online tools were used to analyze the potential target microRNAs of ATGL. The mechanism through which hsa-miR-214-3p regulates ATGL was detected by western blotting, proliferation assays, flow cytometry, and dual-luciferase reporter assays. Our results showed that ATGL was overexpressed in AML cell lines. Moreover, ATGL promoted the growth of AML cells. Additionally, hsa-miR-214-3p could suppress ATGL. Finally, we show that hsa-miR-214-3p regulates ATGL through the hsa-miR-214-3p/ATGL/PPARα pathway. This study showed that hsa-miR-214-3p-regulates aberrant lipolysis by promoting ATGL expression, which causes AML progression through the PPARα pathway.
Keywords: AML; Lipolysis; PPARα; hsa-miR-214-3p; pnpla2/ATGL.
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