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Updated: Jun 20, 2025
Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry
Published on: April 21, 2022
METTL14-mediated N6-methyladenosine modification of TCP1 mRNA promotes acute myeloid leukemia progression
Mengmeng Zhang1, Zhibin Xie1, Yuanyuan Tan1
1Department of Hematology, First Affiliated Hospital of Bengbu Medical University, Anhui Province, China.
Background:
Acute myeloid leukemia (AML) is a prevalent hematologic malignancy characterized by a steady rise in morbidity and mortality rates over time. The upregulation of methyltransferase-like 14 (METTL14) expression in AML has been identified; however, its specific contributions to AML progression and underlying molecular mechanisms have yet to be elucidated.
Method:
METTL14-bound mRNAs were predicted using bioinformatics methods, analyzed, and screened to identify T-complex protein 1 (TCP1). The regulatory impact of METTL14 on TCP1 was observed. TCP1 expression in AML clinical samples was assessed using quantitative real-time PCR and western blot analysis. The involvement of TCP1 in AML malignant progression was assessed through in vitro and in vivo functional assays. The String database was utilized for predicting proteins that interact with TCP1, while western blot assays and immunoprecipitation were employed to validate the associated signaling pathways.
Results:
METTL14 overexpression upregulates TCP1 expression in AML cells. AML patients exhibit high levels of TCP1 expression. Elevated TCP1 levels in HL60 and U937 cells in vitro lead to increased proliferation, migration, invasion, and inhibition of apoptosis, while in vivo, it accelerates AML proliferation and tumorigenesis. Mechanistically, METTL14 modulates AML progression by influencing TCP1 transcript stability via m6A methylation, thereby regulating TCP1 expression. Additionally, PPP2R2C potentially serves as a crucial functional target of TCP1 implicated in the malignant progression of AML.
Conclusion:
Upregulation of TCP1 expression in AML through METTL14-mediated m6A modification accelerates the malignant progression of the disease. Therefore, targeting the m6A modification of TCP1 could be a potential therapeutic strategy to enhance the treatment of AML.
Insights
Methyltransferase-like 14 (METTL14) promotes acute myeloid leukemia (AML) progression by increasing T-complex protein 1 (TCP1) levels via m6A modification. Targeting this pathway offers a potential therapeutic strategy for AML treatment.
Area of Science:
- Hematologic Malignancies
- Molecular Oncology
- Epigenetics
Background:
- Acute myeloid leukemia (AML) is a significant hematologic malignancy with increasing mortality.
- Methyltransferase-like 14 (METTL14) is upregulated in AML, but its role in disease progression is unclear.
Purpose of the Study:
- To elucidate the role of METTL14 in AML progression.
- To identify molecular mechanisms linking METTL14 to AML pathogenesis.
Main Methods:
- Bioinformatic analysis to identify METTL14 targets.
- Quantitative real-time PCR and western blot to assess T-complex protein 1 (TCP1) expression.
- In vitro and in vivo functional assays to evaluate TCP1's role in AML.
- String database and immunoprecipitation to identify interacting proteins and signaling pathways.
Main Results:
- METTL14 overexpression increases TCP1 expression in AML cells and patient samples.
- Elevated TCP1 promotes AML cell proliferation, migration, invasion, and inhibits apoptosis.
- METTL14 regulates TCP1 stability through m6A methylation, driving AML progression.
- PPP2R2C is identified as a potential functional target of TCP1 in AML.
Conclusions:
- METTL14-mediated m6A modification of TCP1 accelerates AML progression.
- Targeting TCP1 m6A modification represents a potential therapeutic strategy for AML.
