FLOT1 knockdown inhibits growth of AML cells through triggering apoptosis and pyroptosis

Ann Hematol. 2023 Mar;102(3):583-595. doi: 10.1007/s00277-023-05103-x. Epub 2023 Jan 26.

Abstract

Acute myeloid leukemia (AML) is a group of hematological malignancies characterized by clonal proliferation of immature myeloid cells. Lipid rafts are highly organized membrane subdomains enriched in cholesterol, sphingolipids, and gangliosides and play roles in regulating apoptosis through subcellular redistribution. Flotillin1 (FLOT1) is a component and also a marker of lipid rafts and had been reported to be involved in the progression of cancers and played important roles in cell death. However, the role of FLOT1 in AML remains to be explored. In this study, we found that increased expression of FLOT1 was correlated with poor clinical outcome in AML patients. Knockdown of FLOT1 in AML cells not only promoted cell death in vitro but also inhibited malignant cells engraftment in vivo. Mechanically, FLOT1 knockdown triggered apoptosis and pyroptosis. FLOT1 overexpression promoted AML cell growth and apoptosis resistance. Our findings indicate that FLOT1 is a prognostic factor of AML and may be a potential target for AML treatment.

Keywords: AML; Apoptosis; FLOT1; Oncogene; Pyroptosis.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Leukemia, Myeloid, Acute* / pathology
  • MicroRNAs*
  • Pyroptosis

Substances

  • MicroRNAs
  • flotillins