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METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification
N(6)-Methyladenosine (m(6)A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N(6) nitrogen of adenosine. However, the roles of m(6)A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltra...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057159/ https://www.ncbi.nlm.nih.gov/pubmed/32145676 http://dx.doi.org/10.1016/j.omtn.2020.01.033 |
Sumario: | N(6)-Methyladenosine (m(6)A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N(6) nitrogen of adenosine. However, the roles of m(6)A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3′ UTR (near to stop codon) of the c-Myc transcript to install the m(6)A modification, thereby enhancing its stability. Furthermore, results revealed that YTH N(6)-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m(6)A-increased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated m(6)A modification, thereby giving rise to OSCC tumorigenesis. |
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