RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer

BACKGROUND: N(6)-methyladenosine is the most abundant eukaryotic mRNA modification and alters a wide range of cellular processes in cancer. Therefore, defining the molecular details are critical for understanding the regulatory mechanism of m(6)A modification. RESULTS: We found that METTL3, a core m...

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Detalles Bibliográficos
Autores principales: Yu, Tao, Wu, Fuxia, Jia, Yan, Zhang, Xue, Qi, Xiaozhen, Jin, Zeyuan, Hao, Tongxin, Zhao, Jianing, Liu, Ziyu, Wang, Chaokun, Niu, Minmin, Yue, Qin, Li, Min, Liu, Yankun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790124/
https://www.ncbi.nlm.nih.gov/pubmed/36566195
http://dx.doi.org/10.1186/s13578-022-00937-w
Descripción
Sumario:BACKGROUND: N(6)-methyladenosine is the most abundant eukaryotic mRNA modification and alters a wide range of cellular processes in cancer. Therefore, defining the molecular details are critical for understanding the regulatory mechanism of m(6)A modification. RESULTS: We found that METTL3, a core m(6)A methyltransferase component, is upregulated and functions as an oncogene in cervical cancer. Mechanistically, METTL3 induces the degradation of m(6)A-modified transcripts of NR4A1 though YTHDF2-DDX6 pathway. In addition, NR4A1 overexpression attenuates the malignant progression through recruiting the LSD1/HDAC1/CoREST transcriptional repression complex to AKT1 promoter. CONCLUSIONS: Our findings reveal that m(6)A regulates cervical cancer cellular progression through manipulating NR4A1 pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-022-00937-w.

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