Related Experiment Video
Updated: Jan 11, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
WTAP-mediated m6A modification of PRMT1 regulates cuproptosis to promote anaplastic thyroid carcinoma progression
Guoli Feng1, Changju Chen2, Yi Luo1
1Department of General Surgery, Affiliated Hospital of Zunyi Medical University, China; Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, China.
Background:
Anaplastic thyroid carcinoma (ATC) is an exceptionally aggressive thyroid cancer subtype. Protein arginine methyltransferases (PRMTs), particularly PRMT1, have emerged as key regulators in cancer biology. This study investigates the therapeutic potential of targeting PRMT1 as a novel strategy for ATC intervention.
Methods:
ATC samples were stratified into high and low PRMT1 expression groups based on PRMT1 levels. Dot blot assay was utilized to assess m6A methylation levels, while RT-PCR quantified the level of m6A-related proteins. Pearson correlation analysis evaluated the relationship between PRMT1 and Wilms'tumor 1-associating protein (WTAP) expression. Mitochondrial membrane potential was measured using the TMRE probe, and Western blotting was used to analyze cuproptosis markers. The m6A modification level of PRMT1 was determined via meRIP-qPCR. Additionally, a xenograft tumor model was established to validate the role of the PRMT1/WTAP pathway in vivo.
Results:
The mRNA and protein expressions of PRMT1 were significantly upregulated in ATC clinical samples and cell lines compared to normal controls. ATC samples were stratified into high and low PRMT1 expression groups using the median PRMT1 protein expression level (determined by immunohistochemistry) as the cutoff. Elevated m6A modification levels were observed in the high PRMT1 expression group. A positive correlation was identified between PRMT1 and WTAP mRNA expression in ATC clinical samples. In vitro studies demonstrated that PRMT1 regulates cuproptosis as the primary mode of cell death in ATC. PRMT1 silencing led to a reduction in mitochondrial membrane potential and increased expression of cuproptosis markers. WTAP knockdown reduced the m6A modification of PRMT1 and decreased its mRNA stability.
Conclusion:
WTAP regulated the m6A modification and mRNA stability of PRMT1. The WTAP/PRMT1 signaling axis modulated cuproptosis, thereby influencing ATC progression. These findings highlighted the potential of targeting the WTAP/PRMT1 pathway as a therapeutic strategy for ATC.
Insights
Targeting Protein Arginine Methyltransferase 1 (PRMT1) and Wilms' tumor 1-associating protein (WTAP) may offer a new therapeutic strategy for anaplastic thyroid carcinoma (ATC). This pathway regulates cell death, impacting ATC progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive cancer.
- Protein arginine methyltransferases (PRMTs), especially PRMT1, are crucial in cancer development.
- This study explores targeting PRMT1 for ATC treatment.
Purpose of the Study:
- To investigate the role of PRMT1 in ATC.
- To explore the therapeutic potential of targeting the PRMT1/WTAP pathway in ATC.
Main Methods:
- Assessed PRMT1 and WTAP expression in ATC samples.
- Measured m6A methylation levels and cuproptosis markers.
- Utilized RT-PCR, Western blotting, and a xenograft model.
Main Results:
- PRMT1 expression is elevated in ATC.
- Higher PRMT1 correlates with increased m6A modification.
- PRMT1 regulates cuproptosis, a key cell death mechanism in ATC.
- WTAP influences PRMT1's m6A modification and mRNA stability.
Conclusions:
- WTAP affects PRMT1 stability and modification.
- The WTAP/PRMT1 pathway controls cuproptosis and ATC progression.
- Targeting the WTAP/PRMT1 axis is a potential therapeutic strategy for ATC.
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