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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...

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Autores principales: Wang, Chuang, Kadigamuwa, Chamila, Wu, Songlv, Gao, Yijun, Chen, Wuya, Gu, Yangcong, Wang, Shengli, Li, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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