ZEB1 serves as an oncogene in acute myeloid leukaemia via regulating the PTEN/PI3K/AKT signalling pathway by combining with P53

J Cell Mol Med. 2021 Jun;25(11):5295-5304. doi: 10.1111/jcmm.16539. Epub 2021 May 7.


Acute myeloid leukaemia is a complex, highly aggressive hematopoietic disorder. Currently, in spite of great advances in radiotherapy and chemotherapy, the prognosis for AML patients with initial treatment failure is still poor. Therefore, the need for novel and efficient therapies to improve AML treatment outcome has become desperately urgent. In this study, we identified the expression of ZEB1 (a transcription factor) and focused on its possible role and mechanisms in the progression of AML. According to the data provided by the Gene Expression Profiling Interactive Analysis (GEPIA), high expression of ZEB1 closely correlates with poor prognosis in AML patients. Additionally, the overexpression of ZEB1 was observed in both AML patients and cell lines. Further functional experiments showed that ZEB1 depletion can induce AML differentiation and inhibit AML proliferation in vitro and in vivo. Moreover, ZEB1 expression was negatively correlated with tumour suppressor P53 expression and ZEB1 can directly bind to P53. Our results also revealed that ZEB1 can regulate PTEN/PI3K/AKT signalling pathway. The inhibitory effect of ZEB1 silencing on PTEN/PI3K/AKT signalling pathway could be significantly reversed by P53 small interfering RNA treatment. Overall, the present data indicated that ZEB1 may be a promising therapeutic target for AML treatment or a potential biomarker for diagnosis and prognosis.

Keywords: AKT pathway; P53; PI3K; PTEN; ZEB1; acute myeloid leukaemia; differentiation; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle
  • Cell Differentiation
  • Cell Proliferation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Xenograft Model Antitumor Assays
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*


  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human