Nicotine-derived NNK promotes CRC progression through activating TMUB1/AKT pathway in METTL14/YTHDF2-mediated m6A manner
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View abstract on PubMed
Summary
This summary is machine-generated.Cigarette smoking promotes colorectal cancer progression. NNK, a carcinogen, upregulates TMUB1 via N6-adenosine methylation, driving invasion and metastasis, suggesting TMUB1 as a therapeutic target.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Colorectal cancer (CRC) is significantly influenced by cigarette smoking, but the molecular mechanisms driving its progression are not fully understood.
- Investigating the link between smoking and CRC revealed correlations with larger tumor size, poor differentiation, and increased invasion.
Purpose Of The Study
- To elucidate the molecular mechanisms by which cigarette smoking, specifically NNK, promotes colorectal cancer progression.
- To identify potential therapeutic and prognostic targets for smoking-related colorectal cancer.
Main Methods
- Analysis of 662 colorectal cancer patients' data.
- In vivo and in vitro experiments using NNK.
- Methylated RNA immunoprecipitation and transcriptome sequencing.
- Investigation of TMUB1, METTL14, and YTHDF2 interactions.
Main Results
- NNK significantly promotes colorectal cancer progression.
- NNK upregulates TMUB1 expression through METTL14/YTHDF2-mediated N6-adenosine methylation.
- Elevated TMUB1 levels correlate with increased invasion, metastasis, and mortality risk in CRC patients.
- TMUB1 promotes AKT ubiquitination, driving malignant proliferation and metastasis.
Conclusions
- The study identifies a novel molecular pathway involving NNK, N6-adenosine methylation, TMUB1, and AKT ubiquitination in colorectal cancer progression.
- Targeting TMUB1 expression via METTL14/YTHDF2-mediated methylation presents a potential therapeutic strategy for smokers with colorectal cancer.
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