NADH dehydrogenase subunit 1/4/5 promotes survival of acute myeloid leukemia by mediating specific oxidative phosphorylation

Mol Med Rep. 2022 Jun;25(6):195. doi: 10.3892/mmr.2022.12711. Epub 2022 Apr 15.

Abstract

Acute myeloid leukemia (AML) is a type of hematological malignancy caused by uncontrolled clonal proliferation of hematopoietic stem cells. The special energy metabolism mode of AML relying on oxidative phosphorylation is different from the traditional 'Warburg effect'. However, its mechanism is not clear. In the present study, it was demonstrated that the mRNA expression levels of NADH dehydrogenase subunit 1, 4 and 5 (ND1, ND4 and ND5) were upregulated in AML samples from The Cancer Genome Atlas database using the limma package in the R programming language. Reverse transcription‑quantitative PCR and ELISA were used to verify the upregulation of ND1, ND4 and ND5 in clinical samples. Pan‑cancer analysis revealed that the expression of ND1 was upregulated only in AML, ND2 was upregulated only in AML and thymoma, and ND4 was upregulated only in AML and kidney chromophobe. In the present study, it was demonstrated that silencing of ND1/4/5 could inhibit the proliferation of AML cells in transplanted tumor of nude mice. Additionally, it was found that oxidative phosphorylation and energy metabolism of AML cells were decreased after silencing of ND1/4/5. In conclusion, the present study suggested that ND1/4/5 may be involved in the regulation of oxidative phosphorylation metabolism in AML as a potential cancer‑promoting factor.

Keywords: NADH dehydrogenase subunit 1/4/5; acute myeloid leukemia; oxidative phosphorylation; proliferation.

MeSH terms

  • Animals
  • Leukemia, Myeloid, Acute* / metabolism
  • Mice
  • Mice, Nude
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism
  • Oxidative Phosphorylation*
  • Up-Regulation

Substances

  • NADH Dehydrogenase

Grants and funding

This work was supported by The Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province (grant no. 2017DG004), The Joint Special Program of Applied Basic Research of Kunming Medical University Young Doctor Program (grant no. 202001AY070001-153) and The Kunming Health Research Project (grant no. 2020-21-01-111).