New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC
Non-alcoholic fatty liver disease (NAFLD) has become a major chronic disease in contemporary society, affected by N6-methyladenosine (m6A) RNA methylation, one of the most common RNA modifications. Compared with healthy control, m6A RNA methyltransferase 3 (METTL3) and METTL14 increased, while Wilms...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.973116/full |
| _version_ | 1797999782610862080 |
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| author | Wenli Cheng Min Li Luyun Zhang Cheng Zhou Susu Yu Xinyue Peng Wenji Zhang Wenjuan Zhang |
| author_facet | Wenli Cheng Min Li Luyun Zhang Cheng Zhou Susu Yu Xinyue Peng Wenji Zhang Wenjuan Zhang |
| author_sort | Wenli Cheng |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD) has become a major chronic disease in contemporary society, affected by N6-methyladenosine (m6A) RNA methylation, one of the most common RNA modifications. Compared with healthy control, m6A RNA methyltransferase 3 (METTL3) and METTL14 increased, while Wilms tumor 1-associated protein (WTAP) and RNA-binding motif protein 15 (RBM15) decreased significantly in NAFLD, and the m6A demethylases fat mass and obesity-associated protein (FTO) elevated. Meanwhile, the m6A binding proteins, YT521-B homology (YTH) domain-containing 1 (YTHDC1), YTHDC2, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), and HNRNPA2B1 were decreased, while eukaryotic translation initiation factor 3 subunit H (EIF3H) was increased significantly. All these changes of m6A regulators had significant differences between healthy control and NAFLD, but no differences between the NAFL and NASH group. The expression level of RBM15, HNRNPC, and HNRNPA2B1 were related to body fat index. RBM15, YTHDC2, HNRNPC, HNRNPA2B1, and EIF3H were related to steatosis. Also, KIAA1429 and YTH domain family 1 (YTHDF1) were related to lobular inflammation. Taken together, m6A regulators were involved in the occurrence of NAFLD. More importantly, abnormal MYC was determined as a key link to m6A regulation of NAFLD. The higher MYC mRNA level was accompanied by higher HDL cholesterol and unsaturated fatty acid proportions, as well as lower fat mass, glucose, and transaminase. Taken together, dysregulation of m6A methylation caused steatosis and fibrosis, affecting the occurrence of NAFLD, and MYC might be its potential target. |
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| language | English |
| last_indexed | 2024-04-11T11:10:14Z |
| publishDate | 2022-08-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-fb8881986d22414990fde655a2c7e81c2022-12-22T04:27:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.973116973116New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYCWenli Cheng0Min Li1Luyun Zhang2Cheng Zhou3Susu Yu4Xinyue Peng5Wenji Zhang6Wenjuan Zhang7Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Provincial Engineering and Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Crops Research Institute, Guangdong Academy of Agricultural Science, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaNon-alcoholic fatty liver disease (NAFLD) has become a major chronic disease in contemporary society, affected by N6-methyladenosine (m6A) RNA methylation, one of the most common RNA modifications. Compared with healthy control, m6A RNA methyltransferase 3 (METTL3) and METTL14 increased, while Wilms tumor 1-associated protein (WTAP) and RNA-binding motif protein 15 (RBM15) decreased significantly in NAFLD, and the m6A demethylases fat mass and obesity-associated protein (FTO) elevated. Meanwhile, the m6A binding proteins, YT521-B homology (YTH) domain-containing 1 (YTHDC1), YTHDC2, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), and HNRNPA2B1 were decreased, while eukaryotic translation initiation factor 3 subunit H (EIF3H) was increased significantly. All these changes of m6A regulators had significant differences between healthy control and NAFLD, but no differences between the NAFL and NASH group. The expression level of RBM15, HNRNPC, and HNRNPA2B1 were related to body fat index. RBM15, YTHDC2, HNRNPC, HNRNPA2B1, and EIF3H were related to steatosis. Also, KIAA1429 and YTH domain family 1 (YTHDF1) were related to lobular inflammation. Taken together, m6A regulators were involved in the occurrence of NAFLD. More importantly, abnormal MYC was determined as a key link to m6A regulation of NAFLD. The higher MYC mRNA level was accompanied by higher HDL cholesterol and unsaturated fatty acid proportions, as well as lower fat mass, glucose, and transaminase. Taken together, dysregulation of m6A methylation caused steatosis and fibrosis, affecting the occurrence of NAFLD, and MYC might be its potential target.https://www.frontiersin.org/articles/10.3389/fphar.2022.973116/fullnon-alcoholic fatty liver disease (NAFLD)non-alcoholic steatohepatitis (NASH)N6-methyladenosine (m6A)RNA methylationMYC |
| spellingShingle | Wenli Cheng Min Li Luyun Zhang Cheng Zhou Susu Yu Xinyue Peng Wenji Zhang Wenjuan Zhang New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC Frontiers in Pharmacology non-alcoholic fatty liver disease (NAFLD) non-alcoholic steatohepatitis (NASH) N6-methyladenosine (m6A) RNA methylation MYC |
| title | New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC |
| title_full | New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC |
| title_fullStr | New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC |
| title_full_unstemmed | New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC |
| title_short | New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC |
| title_sort | new roles of n6 methyladenosine methylation system regulating the occurrence of non alcoholic fatty liver disease with n6 methyladenosine modified myc |
| topic | non-alcoholic fatty liver disease (NAFLD) non-alcoholic steatohepatitis (NASH) N6-methyladenosine (m6A) RNA methylation MYC |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.973116/full |
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