MitoAMPK inhibits the Warburg effect by MZF1-SIRT6 with glycosis related genes in NSCLC

Shangyu Li1, Jinyao He1,2, Lijie Zhang1

  • 1Institute of Hematological Research, Shaanxi Provincial People's Hospital, Xi'an, China.

Insights

Mitochondrial AMPK inhibits the Warburg effect in non-small-cell lung cancer by regulating the MZF1-SIRT6 complex, impacting glycolysis-related genes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • The Warburg effect is a hallmark of cancer, promoting tumor growth.
  • Mitochondrial AMPK (mitoAMPK) is known to inhibit the Warburg effect.
  • The precise mechanisms of mitoAMPK in non-small-cell lung cancer (NSCLC) require further elucidation.

Purpose of the Study:

  • To investigate the role of SIRT6 and MZF1 in the mechanism by which mitoAMPK inhibits the Warburg effect in NSCLC.
  • To clarify the molecular interactions and regulatory pathways involved.

Main Methods:

  • Western blotting and quantitative polymerase chain reaction (qPCR) to assess protein and gene expression.
  • Cell Counting Kit-8 (CCK-8) assay for cell proliferation.
  • Immunohistochemistry assays for tissue analysis.
  • Chromatin immunoprecipitation (ChIP)-qPCR to confirm protein-DNA interactions.

Main Results:

  • SIRT6 expression was significantly lower in NSCLC tissues and cell lines compared to normal controls.
  • SIRT6 inhibited the Warburg effect by downregulating glycolysis-related genes: SLC2A2, SLC2A4, and PKM2.
  • A direct interaction between SIRT6 and MZF1 was confirmed.

Conclusions:

  • MitoAMPK inhibits the Warburg effect in NSCLC.
  • This inhibition is mediated through the regulation of the MZF1-SIRT6 complex.
  • SIRT6 acts as a key regulator in this pathway, impacting key glycolytic genes.

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