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ATF4/MYC Regulates MTHFD2 to Promote NSCLC Progression by Mediating Redox Homeostasis
Yixing Gao1,2, Lan Feng3,4,5, Luping Zhang6
1Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, China.
Disease Markers
|September 2, 2022
Summary
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) drives non-small-cell lung cancer (NSCLC) progression by increasing oxidative stress. ATF4 promotes MTHFD2 expression via MYC, highlighting a potential therapeutic target for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is overexpressed in non-small-cell lung cancer (NSCLC), correlating with tumor proliferation.
- The precise mechanisms driving MTHFD2 overexpression in NSCLC remain unclear.
Purpose of the Study:
- To elucidate the regulatory mechanism of MTHFD2 expression in NSCLC.
- To investigate the role of MTHFD2 in NSCLC progression and its relationship with oxidative stress.
Main Methods:
- Quantitative PCR, Western blot, and immunofluorescence to assess MTHFD2 expression.
- Flow cytometry and TUNEL assays for apoptosis and cell cycle analysis.
- Dual-luciferase reporter assays to determine transcriptional regulation by ATF4 and MYC.
Main Results:
- MTHFD2 is highly expressed in NSCLC cells, and its knockdown inhibits proliferation and increases apoptosis.
- MTHFD2 knockdown alters redox balance, increasing oxidative factors and decreasing antioxidant factors.
- ATF4 promotes MTHFD2 transcription indirectly through MYC, not via direct interaction.
Conclusions:
- ATF4 stimulates MTHFD2 expression in NSCLC through MYC-mediated transcriptional regulation.
- MTHFD2 plays a critical role in NSCLC progression via the redox pathway, making it a potential therapeutic target.
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