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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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
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author 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
author_facet 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
author_sort Yu, Tao
collection PubMed
description 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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spelling pubmed-97901242022-12-26 RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer 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 Cell Biosci Research 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. BioMed Central 2022-12-25 /pmc/articles/PMC9790124/ /pubmed/36566195 http://dx.doi.org/10.1186/s13578-022-00937-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
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
RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer
title RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer
title_full RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer
title_fullStr RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer
title_full_unstemmed RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer
title_short RNA N(6)-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer
title_sort rna n(6)-methyladenosine modification mediates downregulation of nr4a1 to facilitate malignancy of cervical cancer
topic Research
url 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
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