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RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma
Background: Arecoline is known as the main active carcinogen found in areca nut extract that drives the pathological progression of oral squamous cell carcinoma (OSCC). Studies have revealed that dysregulation of RNA N6-methyladenosine (m6A) methyltransferase components is intimately linked to cance...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688745/ https://www.ncbi.nlm.nih.gov/pubmed/36429032 http://dx.doi.org/10.3390/cells11223605 |
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author | Wang, Chuang Kadigamuwa, Chamila Wu, Songlv Gao, Yijun Chen, Wuya Gu, Yangcong Wang, Shengli Li, Xia |
author_facet | Wang, Chuang Kadigamuwa, Chamila Wu, Songlv Gao, Yijun Chen, Wuya Gu, Yangcong Wang, Shengli Li, Xia |
author_sort | Wang, Chuang |
collection | PubMed |
description | Background: Arecoline is known as the main active carcinogen found in areca nut extract that drives the pathological progression of oral squamous cell carcinoma (OSCC). Studies have revealed that dysregulation of RNA N6-methyladenosine (m6A) methyltransferase components is intimately linked to cancer initiation and progression, including oral cancer. Methods: The arecoline-induced dysregulated methyltransferase-like 3 (METTL3) gene was identified using RNA-seq transcriptome assay. Using in vitro and in vivo models, the biological roles of METTL3 in arecoline-transformed oral cancer were examined. Results: We found that METTL3 was markedly elevated in arecoline-exposed OSCC cell lines and OSCC tissues of areca nut chewers. We identified that hypoxia-inducible factor 1-alpha (HIF-1α) stimulated METTL3 expression at the transcriptional level and further proved that METTL3-MYC-HIF-1α formed a positive autoregulation loop in arecoline-transformed OSCC cells. Subsequently, we manifested that METTL3 depletion profoundly reduced cell proliferation, cell migration, oncogenicity, and cisplatin resistance of arecoline-exposed OSCC cells. Conclusions: Developing novel strategies to target METTL3 may be a potential way to treat OSCC patients, particularly those with areca nut chewing history and receiving cisplatin treatment. |
format | Online Article Text |
id | pubmed-9688745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96887452022-11-25 RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma Wang, Chuang Kadigamuwa, Chamila Wu, Songlv Gao, Yijun Chen, Wuya Gu, Yangcong Wang, Shengli Li, Xia Cells Article Background: Arecoline is known as the main active carcinogen found in areca nut extract that drives the pathological progression of oral squamous cell carcinoma (OSCC). Studies have revealed that dysregulation of RNA N6-methyladenosine (m6A) methyltransferase components is intimately linked to cancer initiation and progression, including oral cancer. Methods: The arecoline-induced dysregulated methyltransferase-like 3 (METTL3) gene was identified using RNA-seq transcriptome assay. Using in vitro and in vivo models, the biological roles of METTL3 in arecoline-transformed oral cancer were examined. Results: We found that METTL3 was markedly elevated in arecoline-exposed OSCC cell lines and OSCC tissues of areca nut chewers. We identified that hypoxia-inducible factor 1-alpha (HIF-1α) stimulated METTL3 expression at the transcriptional level and further proved that METTL3-MYC-HIF-1α formed a positive autoregulation loop in arecoline-transformed OSCC cells. Subsequently, we manifested that METTL3 depletion profoundly reduced cell proliferation, cell migration, oncogenicity, and cisplatin resistance of arecoline-exposed OSCC cells. Conclusions: Developing novel strategies to target METTL3 may be a potential way to treat OSCC patients, particularly those with areca nut chewing history and receiving cisplatin treatment. MDPI 2022-11-14 /pmc/articles/PMC9688745/ /pubmed/36429032 http://dx.doi.org/10.3390/cells11223605 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Chuang Kadigamuwa, Chamila Wu, Songlv Gao, Yijun Chen, Wuya Gu, Yangcong Wang, Shengli Li, Xia RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma |
title | RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma |
title_full | RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma |
title_fullStr | RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma |
title_full_unstemmed | RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma |
title_short | RNA N6-Methyladenosine (m6A) Methyltransferase-like 3 Facilitates Tumorigenesis and Cisplatin Resistance of Arecoline-Exposed Oral Carcinoma |
title_sort | rna n6-methyladenosine (m6a) methyltransferase-like 3 facilitates tumorigenesis and cisplatin resistance of arecoline-exposed oral carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688745/ https://www.ncbi.nlm.nih.gov/pubmed/36429032 http://dx.doi.org/10.3390/cells11223605 |
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