GIPC2 is a tumor suppressor gene for acute myeloid leukemia and induces apoptosis of leukemia cells by regulating the PI3K/AKT pathway

Epigenomics. 2023 Mar;15(6):369-383. doi: 10.2217/epi-2023-0027. Epub 2023 May 22.

Abstract

Aims: To explore the expression and methylation levels of GIPC2 in acute myeloid leukemia (AML), discuss the mechanism of GIPC2 in AML and provide new strategies for the diagnosis and treatment of AML. Methods: qPCR, western blotting, cell counting kit-8 assay, bisulfite sequencing and other experiments were used in this study. Results: The expression of GIPC2 was found to be downregulated in AML and is mainly affected by DNA promoter methylation. Decitabine can demethylate the promoter region of GIPC2, and GIPC2 expression is upregulated after demethylation. Overexpression of GIPC2 in HL-60 cells can induce apoptosis by inhibiting the PI3K/AKT pathway. Conclusion: Our findings identify that GIPC2 is associated with the PI3K/AKT signaling pathway and may represent a potential therapeutic target and biomarker for the management of AML.

Keywords: AML; GIPC2; PI3K/AKT; apoptosis; methylation.

MeSH terms

  • Apoptosis / genetics
  • Carrier Proteins / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Genes, Tumor Suppressor
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • GIPC2 protein, human
  • Carrier Proteins