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Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver

MiR-143 play an important role in hepatocellular carcinoma and liver fibrosis via inhibiting hepatoma cell proliferation. DNA methyltransferase 3 alpha (DNMT3a), as a target of miR-143, regulates the development of primary organic solid tumors through DNA methylation mechanisms. However, the effect...

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Autores principales: Chen, Xingping, Luo, Junyi, Liu, Jie, Chen, Ting, Sun, Jiajie, Zhang, Yongliang, Xi, Qianyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658369/
https://www.ncbi.nlm.nih.gov/pubmed/34884879
http://dx.doi.org/10.3390/ijms222313075
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author Chen, Xingping
Luo, Junyi
Liu, Jie
Chen, Ting
Sun, Jiajie
Zhang, Yongliang
Xi, Qianyun
author_facet Chen, Xingping
Luo, Junyi
Liu, Jie
Chen, Ting
Sun, Jiajie
Zhang, Yongliang
Xi, Qianyun
author_sort Chen, Xingping
collection PubMed
description MiR-143 play an important role in hepatocellular carcinoma and liver fibrosis via inhibiting hepatoma cell proliferation. DNA methyltransferase 3 alpha (DNMT3a), as a target of miR-143, regulates the development of primary organic solid tumors through DNA methylation mechanisms. However, the effect of miR-143 on DNA methylation profiles in liver is unclear. In this study, we used Whole-Genome Bisulfite Sequencing (WGBS) to detect the differentially methylated regions (DMRs), and investigated DMR-related genes and their enriched pathways by miR-143. We found that methylated cytosines increased 0.19% in the miR-143 knock-out (KO) liver fed with high-fat diet (HFD), compared with the wild type (WT). Furthermore, compared with the WT group, the CG methylation patterns of the KO group showed lower CG methylation levels in CG islands (CGIs), promoters and hypermethylation in CGI shores, 5′UTRs, exons, introns, 3′UTRs, and repeat regions. A total of 984 DMRs were identified between the WT and KO groups consisting of 559 hypermethylation and 425 hypomethylation DMRs. Furthermore, DMR-related genes were enriched in metabolism pathways such as carbon metabolism (serine hydroxymethyltransferase 2 (Shmt2), acyl-Coenzyme A dehydrogenase medium chain (Acadm)), arginine and proline metabolism (spermine synthase (Sms), proline dehydrogenase (Prodh2)) and purine metabolism (phosphoribosyl pyrophosphate synthetase 2 (Prps2)). In summary, we are the first to report the change in whole-genome methylation levels by miR-143-null through WGBS in mice liver, and provide an experimental basis for clinical diagnosis and treatment in liver diseases, indicating that miR-143 may be a potential therapeutic target and biomarker for liver damage-associated diseases and hepatocellular carcinoma.
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spelling pubmed-86583692021-12-10 Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver Chen, Xingping Luo, Junyi Liu, Jie Chen, Ting Sun, Jiajie Zhang, Yongliang Xi, Qianyun Int J Mol Sci Article MiR-143 play an important role in hepatocellular carcinoma and liver fibrosis via inhibiting hepatoma cell proliferation. DNA methyltransferase 3 alpha (DNMT3a), as a target of miR-143, regulates the development of primary organic solid tumors through DNA methylation mechanisms. However, the effect of miR-143 on DNA methylation profiles in liver is unclear. In this study, we used Whole-Genome Bisulfite Sequencing (WGBS) to detect the differentially methylated regions (DMRs), and investigated DMR-related genes and their enriched pathways by miR-143. We found that methylated cytosines increased 0.19% in the miR-143 knock-out (KO) liver fed with high-fat diet (HFD), compared with the wild type (WT). Furthermore, compared with the WT group, the CG methylation patterns of the KO group showed lower CG methylation levels in CG islands (CGIs), promoters and hypermethylation in CGI shores, 5′UTRs, exons, introns, 3′UTRs, and repeat regions. A total of 984 DMRs were identified between the WT and KO groups consisting of 559 hypermethylation and 425 hypomethylation DMRs. Furthermore, DMR-related genes were enriched in metabolism pathways such as carbon metabolism (serine hydroxymethyltransferase 2 (Shmt2), acyl-Coenzyme A dehydrogenase medium chain (Acadm)), arginine and proline metabolism (spermine synthase (Sms), proline dehydrogenase (Prodh2)) and purine metabolism (phosphoribosyl pyrophosphate synthetase 2 (Prps2)). In summary, we are the first to report the change in whole-genome methylation levels by miR-143-null through WGBS in mice liver, and provide an experimental basis for clinical diagnosis and treatment in liver diseases, indicating that miR-143 may be a potential therapeutic target and biomarker for liver damage-associated diseases and hepatocellular carcinoma. MDPI 2021-12-03 /pmc/articles/PMC8658369/ /pubmed/34884879 http://dx.doi.org/10.3390/ijms222313075 Text en © 2021 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
Chen, Xingping
Luo, Junyi
Liu, Jie
Chen, Ting
Sun, Jiajie
Zhang, Yongliang
Xi, Qianyun
Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver
title Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver
title_full Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver
title_fullStr Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver
title_full_unstemmed Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver
title_short Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver
title_sort exploration of the effect on genome-wide dna methylation by mir-143 knock-out in mice liver
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658369/
https://www.ncbi.nlm.nih.gov/pubmed/34884879
http://dx.doi.org/10.3390/ijms222313075
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