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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 |
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author | Zhao, Wei Cui, Yameng Liu, Lina Ma, Xiaozhou Qi, Xiaoqian Wang, Yue Liu, Zihao Ma, Shiqing Liu, Jingwen Wu, Jie |
author_facet | Zhao, Wei Cui, Yameng Liu, Lina Ma, Xiaozhou Qi, Xiaoqian Wang, Yue Liu, Zihao Ma, Shiqing Liu, Jingwen Wu, Jie |
author_sort | Zhao, Wei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7057159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-70571592020-03-09 METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification Zhao, Wei Cui, Yameng Liu, Lina Ma, Xiaozhou Qi, Xiaoqian Wang, Yue Liu, Zihao Ma, Shiqing Liu, Jingwen Wu, Jie Mol Ther Nucleic Acids Article 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. American Society of Gene & Cell Therapy 2020-02-04 /pmc/articles/PMC7057159/ /pubmed/32145676 http://dx.doi.org/10.1016/j.omtn.2020.01.033 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Zhao, Wei Cui, Yameng Liu, Lina Ma, Xiaozhou Qi, Xiaoqian Wang, Yue Liu, Zihao Ma, Shiqing Liu, Jingwen Wu, Jie METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification |
title | METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification |
title_full | METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification |
title_fullStr | METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification |
title_full_unstemmed | METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification |
title_short | METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification |
title_sort | mettl3 facilitates oral squamous cell carcinoma tumorigenesis by enhancing c-myc stability via ythdf1-mediated m(6)a modification |
topic | Article |
url | 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 |
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