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Published on: July 21, 2018
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.
Abstract:
MitoAMPK was proved to inhibit the Warburg effect, but the specific mechanisms on non-small-cell lung cancer remain unclear. Here, we selected SIRT6 and MZF1 to clarify the mechanism. By western blotting, quantitative polymerase chain reaction, the CCK-8 assay, and immunohistochemistry assays, we found SIRT6 expression was lower in NSCLC tissues and cell lines than normal tissues and cells. Moreover, SIRT6 could inhibit the Warburg effect by regulating glycolysis-related genes of SLC2A2, SLC2A4 and PKM2. Finally, we demonstrated the interaction between SIRT6 and MZF1 using ChIP-qPCR. In conclusion, mitoAMPK inhibits the Warburg effect by regulating the expression of the MZF1-SIRT6 complex.
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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