AHR signaling pathway mediates mitochondrial oxidative phosphorylation which leads to cytarabine resistance

Acta Biochim Biophys Sin (Shanghai). 2024 Apr 25;56(4):597-606. doi: 10.3724/abbs.2024022.

Abstract

The aryl hydrocarbon receptor (AHR) has been identified as a significant driver of tumorigenesis. However, its clinical significance in acute myeloid leukemia (AML) remains largely unclear. In this study, RNA-Seq data from AML patients (bone marrow samples from 173 newly diagnosed AML patients) obtained from the TCGA database, and normal human RNA-Seq data (bone marrow samples from 70 healthy individuals) obtained from the GTEX database are downloaded for external validation and complementarity. The data analysis reveals that the AHR signaling pathway is activated in AML patients. Furthermore, there is a correlation between the expressions of AHR and mitochondrial oxidative phosphorylation genes. In vitro experiments show that enhancing AHR expression in AML cells increases mitochondrial oxidative phosphorylation and induces resistance to cytarabine. Conversely, reducing AHR expression in AML cells decreases cytarabine resistance. These findings deepen our understanding of the AHR signaling pathway's involvement in AML.

Keywords: AHR expression; AML; cytarabine resistance; mitochondrial oxidative phosphorylation.

MeSH terms

  • Cytarabine* / pharmacology
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Oxidative Phosphorylation
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Signal Transduction

Substances

  • Cytarabine
  • Receptors, Aryl Hydrocarbon

Grants and funding

This work was supported by the grants from the Youth Program of the Natural Science Foundation of Shangdong Province (No. ZR2022QH239), PhD Research Foundation of Affiliated Hospital of Jining Medical University (2022-BS-007) and the “Nursery” Research Program of Affiliated Hospital of Jining Medical University (MP-ZD-2021-004).