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METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner

BACKGROUND: As the most prevalent chemical modifications on eukaryotic mRNAs, N6-methyladenosine (m6A) methylation was reported to participate in the regulation of various metabolic diseases. This study aimed to investigate the roles of m6A methylation and methyltransferase-like16 (METTL16) in non-a...

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Autores principales: Tang, Jinhong, Zhao, Xiangyun, Wei, Wei, Liu, Weiwei, Fan, Huining, Liu, Xiu ping, Li, Yungai, Wang, Long, Guo, Jinghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744165/
https://www.ncbi.nlm.nih.gov/pubmed/36518278
http://dx.doi.org/10.7717/peerj.14379
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author Tang, Jinhong
Zhao, Xiangyun
Wei, Wei
Liu, Weiwei
Fan, Huining
Liu, Xiu ping
Li, Yungai
Wang, Long
Guo, Jinghui
author_facet Tang, Jinhong
Zhao, Xiangyun
Wei, Wei
Liu, Weiwei
Fan, Huining
Liu, Xiu ping
Li, Yungai
Wang, Long
Guo, Jinghui
author_sort Tang, Jinhong
collection PubMed
description BACKGROUND: As the most prevalent chemical modifications on eukaryotic mRNAs, N6-methyladenosine (m6A) methylation was reported to participate in the regulation of various metabolic diseases. This study aimed to investigate the roles of m6A methylation and methyltransferase-like16 (METTL16) in non-alcoholic fatty liver disease (NAFLD). METHODS: In this study, we used a model of diet-induced NAFLD, maintaining six male C57BL/6J mice on high-fat diet (HFD) to generate hepatic steatosis. The high-throughput sequencing and RNA sequencing were performed to identify the m6A methylation patterns and differentially expressed mRNAs in HFD mice livers. Furthermore, we detected the expression levels of m6A modify enzymes by qRT-PCR in liver tissues, and further investigated the potential role of METTL16 in NAFLD through constructing overexpression and a knockdown model of METTL16 in HepG2 cells. RESULTS: In total, we confirmed 15,999 m6A recurrent peaks in HFD mice and 12,322 in the control. Genes with differentially methylated m6A peaks were significantly associated with the dysregulated glucolipid metabolism and aggravated hepatic inflammatory response. In addition, we identified five genes (CIDEA, THRSP, OSBPL3, GDF15 and LGALS1) that played important roles in NAFLD progression after analyzing the differentially expressed genes containing differentially methylated m6A peaks. Intriguingly, we found that the expression levels of METTL16 were substantially increased in the NAFLD model in vivo and in vitro, and further confirmed that METTL16 upregulated the expression level of lipogenic genes CIDEA in HepG2 cells. CONCLUSIONS: These results indicate the critical roles of m6A methylation and METTL16 in HFD-induced mice and cell NAFLD models, which broaden people’s perspectives on potential m6A-related treatments and biomarkers for NAFLD.
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spelling pubmed-97441652022-12-13 METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner Tang, Jinhong Zhao, Xiangyun Wei, Wei Liu, Weiwei Fan, Huining Liu, Xiu ping Li, Yungai Wang, Long Guo, Jinghui PeerJ Bioinformatics BACKGROUND: As the most prevalent chemical modifications on eukaryotic mRNAs, N6-methyladenosine (m6A) methylation was reported to participate in the regulation of various metabolic diseases. This study aimed to investigate the roles of m6A methylation and methyltransferase-like16 (METTL16) in non-alcoholic fatty liver disease (NAFLD). METHODS: In this study, we used a model of diet-induced NAFLD, maintaining six male C57BL/6J mice on high-fat diet (HFD) to generate hepatic steatosis. The high-throughput sequencing and RNA sequencing were performed to identify the m6A methylation patterns and differentially expressed mRNAs in HFD mice livers. Furthermore, we detected the expression levels of m6A modify enzymes by qRT-PCR in liver tissues, and further investigated the potential role of METTL16 in NAFLD through constructing overexpression and a knockdown model of METTL16 in HepG2 cells. RESULTS: In total, we confirmed 15,999 m6A recurrent peaks in HFD mice and 12,322 in the control. Genes with differentially methylated m6A peaks were significantly associated with the dysregulated glucolipid metabolism and aggravated hepatic inflammatory response. In addition, we identified five genes (CIDEA, THRSP, OSBPL3, GDF15 and LGALS1) that played important roles in NAFLD progression after analyzing the differentially expressed genes containing differentially methylated m6A peaks. Intriguingly, we found that the expression levels of METTL16 were substantially increased in the NAFLD model in vivo and in vitro, and further confirmed that METTL16 upregulated the expression level of lipogenic genes CIDEA in HepG2 cells. CONCLUSIONS: These results indicate the critical roles of m6A methylation and METTL16 in HFD-induced mice and cell NAFLD models, which broaden people’s perspectives on potential m6A-related treatments and biomarkers for NAFLD. PeerJ Inc. 2022-12-01 /pmc/articles/PMC9744165/ /pubmed/36518278 http://dx.doi.org/10.7717/peerj.14379 Text en © 2022 Tang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Tang, Jinhong
Zhao, Xiangyun
Wei, Wei
Liu, Weiwei
Fan, Huining
Liu, Xiu ping
Li, Yungai
Wang, Long
Guo, Jinghui
METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner
title METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner
title_full METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner
title_fullStr METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner
title_full_unstemmed METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner
title_short METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner
title_sort mettl16-mediated translation of cidea promotes non-alcoholic fatty liver disease progression via m6a-dependent manner
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744165/
https://www.ncbi.nlm.nih.gov/pubmed/36518278
http://dx.doi.org/10.7717/peerj.14379
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