Upregulation of ROBO3 promotes proliferation, migration and adhesion of AML cells and affects the survival of AML patients

Biochem Biophys Res Commun. 2023 Jun 18:661:1-9. doi: 10.1016/j.bbrc.2023.04.030. Epub 2023 Apr 14.

Abstract

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, which is the most common and severe acute leukemia in adults. Its occurrence, development and prognosis are affected by many factors, and more research is still needed to further guide its treatment. Here, we found that roundabout3 (ROBO3) was associated with poor prognosis in AML through bioinformatics analysis. We then found that overexpression of ROBO3 promoted AML cell proliferation, adhesion and migration while knockdown of ROBO3 had opposite effects. We subsequently found that ROBO3 regulated CD34 expression in AML cells, and this regulatory effect may be achieved through the Hippo-YAP pathway. The inhibitors of this pathway, K-975 and verteporfin, showed an inhibitory effect on AML cells with high ROBO3 expression. ROBO3 was also found to be significantly increased in bone marrow samples from AML patients. Our research indicates that ROBO3 plays an important role in the development of AML, which suggests that ROBO3 can be a prognostic biomarker and potential therapeutic target for AML.

Keywords: AML; Adhesion; KG-1; Leukemia; Migration; Proliferation; ROBO3; SLIT-ROBO family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Leukemia, Myeloid, Acute* / pathology
  • Receptors, Cell Surface / metabolism
  • Up-Regulation

Substances

  • ROBO3 protein, human
  • Receptors, Cell Surface