Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing
N6-Methyladenosine (m6A), a unique and common mRNA modification method in eukaryotes, is involved in the occurrence and development of many diseases. Liver fibrosis (LF) is a common response to chronic liver injury and may lead to cirrhosis and even liver cancer. However, the involvement of m6A meth...
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2021
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oai:doaj.org-article:1d5740bc6fa046f69f8be21298e5c4102021-11-16T06:43:13ZComprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing2296-634X10.3389/fcell.2021.767051https://doaj.org/article/1d5740bc6fa046f69f8be21298e5c4102021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.767051/fullhttps://doaj.org/toc/2296-634XN6-Methyladenosine (m6A), a unique and common mRNA modification method in eukaryotes, is involved in the occurrence and development of many diseases. Liver fibrosis (LF) is a common response to chronic liver injury and may lead to cirrhosis and even liver cancer. However, the involvement of m6A methylation in the development of LF is still unknown. In this study, we performed a systematic evaluation of hepatic genome-wide m6A modification and mRNA expression by m6A-seq and RNA-seq using LF mice. There were 3,315 genes with significant differential m6A levels, of which 2,498 were hypermethylated and 817 hypomethylated. GO and KEGG analyses illustrated that differentially expressed m6A genes were closely correlated with processes such as the endoplasmic reticulum stress response, PPAR signaling pathway and TGF-β signaling pathway. Moreover, a total of 90 genes had both a significant change in the m6A level and mRNA expression shown by joint analysis of m6A-seq and RNA-seq. Hence, the critical elements of m6A modification, including methyltransferase WTAP, demethylases ALKBH5 and binding proteins YTHDF1 were confirmed by RT-qPCR and Western blot. In an additional cell experiment, we also observed that the decreased expression of WTAP induced the development of LF as a result of promoting hepatic stellate cell (HSC) activation. Therefore, this study revealed unique differential m6A methylation patterns in LF mice and suggested that m6A methylation was associated with the occurrence and course of LF to some extent.Chang FanChang FanYanzhen MaYanzhen MaSen ChenSen ChenQiumei ZhouHui JiangHui JiangHui JiangJiafu ZhangFurong WuFrontiers Media S.A.articlem6A methylationm6A-seqliver fibrosisHSCsWTAPBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021) |
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m6A methylation m6A-seq liver fibrosis HSCs WTAP Biology (General) QH301-705.5 |
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m6A methylation m6A-seq liver fibrosis HSCs WTAP Biology (General) QH301-705.5 Chang Fan Chang Fan Yanzhen Ma Yanzhen Ma Sen Chen Sen Chen Qiumei Zhou Hui Jiang Hui Jiang Hui Jiang Jiafu Zhang Furong Wu Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing |
| description |
N6-Methyladenosine (m6A), a unique and common mRNA modification method in eukaryotes, is involved in the occurrence and development of many diseases. Liver fibrosis (LF) is a common response to chronic liver injury and may lead to cirrhosis and even liver cancer. However, the involvement of m6A methylation in the development of LF is still unknown. In this study, we performed a systematic evaluation of hepatic genome-wide m6A modification and mRNA expression by m6A-seq and RNA-seq using LF mice. There were 3,315 genes with significant differential m6A levels, of which 2,498 were hypermethylated and 817 hypomethylated. GO and KEGG analyses illustrated that differentially expressed m6A genes were closely correlated with processes such as the endoplasmic reticulum stress response, PPAR signaling pathway and TGF-β signaling pathway. Moreover, a total of 90 genes had both a significant change in the m6A level and mRNA expression shown by joint analysis of m6A-seq and RNA-seq. Hence, the critical elements of m6A modification, including methyltransferase WTAP, demethylases ALKBH5 and binding proteins YTHDF1 were confirmed by RT-qPCR and Western blot. In an additional cell experiment, we also observed that the decreased expression of WTAP induced the development of LF as a result of promoting hepatic stellate cell (HSC) activation. Therefore, this study revealed unique differential m6A methylation patterns in LF mice and suggested that m6A methylation was associated with the occurrence and course of LF to some extent. |
| format |
article |
| author |
Chang Fan Chang Fan Yanzhen Ma Yanzhen Ma Sen Chen Sen Chen Qiumei Zhou Hui Jiang Hui Jiang Hui Jiang Jiafu Zhang Furong Wu |
| author_facet |
Chang Fan Chang Fan Yanzhen Ma Yanzhen Ma Sen Chen Sen Chen Qiumei Zhou Hui Jiang Hui Jiang Hui Jiang Jiafu Zhang Furong Wu |
| author_sort |
Chang Fan |
| title |
Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing |
| title_short |
Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing |
| title_full |
Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing |
| title_fullStr |
Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing |
| title_full_unstemmed |
Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing |
| title_sort |
comprehensive analysis of the transcriptome-wide m6a methylation modification difference in liver fibrosis mice by high-throughput m6a sequencing |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/1d5740bc6fa046f69f8be21298e5c410 |
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