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miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6
MicroRNAs have emerged as essential regulators in the biological process of liver regeneration by modulating the post‐transcriptional expression of the target genes. In the present study, we found miR‐20a expression is decreased remarkably in three rodent liver regeneration models using miRNA PCR ar...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178283/ https://www.ncbi.nlm.nih.gov/pubmed/33951279 http://dx.doi.org/10.1111/jcmm.16530 |
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author | Tu, Wei Gong, Jin Song, Jun Tian, Dean Wang, Zhijun |
author_facet | Tu, Wei Gong, Jin Song, Jun Tian, Dean Wang, Zhijun |
author_sort | Tu, Wei |
collection | PubMed |
description | MicroRNAs have emerged as essential regulators in the biological process of liver regeneration by modulating the post‐transcriptional expression of the target genes. In the present study, we found miR‐20a expression is decreased remarkably in three rodent liver regeneration models using miRNA PCR array and Venn diagram analysis. Inhibition of miR‐20a expression enhanced hepatocytes proliferation in vivo and in vitro. In contrast, overexpression of miR‐20a reduces hepatocytes proliferation and subsequently impaired liver regeneration in the mouse PHx model. Moreover, we have identified TCF4 as a target gene of miR‐20a using the PCR Array and luciferase assay. Next, mice with TCF4 deficiency were used to establish the PHx model and subjected to the examination of liver regeneration capacity. We found TCF4‐deficient mice exhibited impaired liver regeneration compared with control. Given that TCF4 acts as a transcription factor, we sort to elucidate the downstream genes involved in liver regeneration. Promoter analysis and Chip assay confirmed that TCF4 enhances CDC2 and CDC6 expression through binding to the promoter region and leads to the proliferation and cell cycle progression in hepatocytes. In conclusion, this study provides evidence that the miR20a‐TCF4‐CDC2/6 axis plays an essential role during liver regeneration. |
format | Online Article Text |
id | pubmed-8178283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81782832021-06-15 miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6 Tu, Wei Gong, Jin Song, Jun Tian, Dean Wang, Zhijun J Cell Mol Med Original Articles MicroRNAs have emerged as essential regulators in the biological process of liver regeneration by modulating the post‐transcriptional expression of the target genes. In the present study, we found miR‐20a expression is decreased remarkably in three rodent liver regeneration models using miRNA PCR array and Venn diagram analysis. Inhibition of miR‐20a expression enhanced hepatocytes proliferation in vivo and in vitro. In contrast, overexpression of miR‐20a reduces hepatocytes proliferation and subsequently impaired liver regeneration in the mouse PHx model. Moreover, we have identified TCF4 as a target gene of miR‐20a using the PCR Array and luciferase assay. Next, mice with TCF4 deficiency were used to establish the PHx model and subjected to the examination of liver regeneration capacity. We found TCF4‐deficient mice exhibited impaired liver regeneration compared with control. Given that TCF4 acts as a transcription factor, we sort to elucidate the downstream genes involved in liver regeneration. Promoter analysis and Chip assay confirmed that TCF4 enhances CDC2 and CDC6 expression through binding to the promoter region and leads to the proliferation and cell cycle progression in hepatocytes. In conclusion, this study provides evidence that the miR20a‐TCF4‐CDC2/6 axis plays an essential role during liver regeneration. John Wiley and Sons Inc. 2021-05-05 2021-06 /pmc/articles/PMC8178283/ /pubmed/33951279 http://dx.doi.org/10.1111/jcmm.16530 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Tu, Wei Gong, Jin Song, Jun Tian, Dean Wang, Zhijun miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6 |
title | miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6 |
title_full | miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6 |
title_fullStr | miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6 |
title_full_unstemmed | miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6 |
title_short | miR‐20a/TCF4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6 |
title_sort | mir‐20a/tcf4 axis‐mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice phx model by regulating cdc2 and cdc6 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178283/ https://www.ncbi.nlm.nih.gov/pubmed/33951279 http://dx.doi.org/10.1111/jcmm.16530 |
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