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Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis

CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carb...

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Autores principales: Yang, Ya-Ru, Hu, Shuang, Bu, Fang-Tian, Li, Hao, Huang, Cheng, Meng, Xiao-Ming, Zhang, Lei, Lv, Xiong-Wen, Li, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648568/
https://www.ncbi.nlm.nih.gov/pubmed/34887753
http://dx.doi.org/10.3389/fphar.2021.741151
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author Yang, Ya-Ru
Hu, Shuang
Bu, Fang-Tian
Li, Hao
Huang, Cheng
Meng, Xiao-Ming
Zhang, Lei
Lv, Xiong-Wen
Li, Jun
author_facet Yang, Ya-Ru
Hu, Shuang
Bu, Fang-Tian
Li, Hao
Huang, Cheng
Meng, Xiao-Ming
Zhang, Lei
Lv, Xiong-Wen
Li, Jun
author_sort Yang, Ya-Ru
collection PubMed
description CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For example, circCREBBP was significantly down-regulated in primary hepatic stellate cells (HSCs) and liver tissue of HF mice induced by CCl4 compared to those in the vehicle group. Overexpression of circCREBBP with AAV8-circCREBBP in vivo prevented CCl4-induced HF worsening by reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents, liver hydroxyproline levels, collagen deposition, and levels of pro-fibrosis genes and pro-inflammatory cytokines. Furthermore, in vitro function loss and function gain analysis showed that circCREBBP inhibited HSCs activation and proliferation. Mechanically, circCREBBP acts as a sponge for hsa-miR-1291 and subsequently promotes LEFTY2 expression. In conclusion, our current results reveal a novel mechanism by which circCREBBP alleviates liver fibrosis by targeting the hsa-miR-1291/LEFTY2 axis, and also suggest that circCREBBP may be a potential biomarker for heart failure.
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spelling pubmed-86485682021-12-08 Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis Yang, Ya-Ru Hu, Shuang Bu, Fang-Tian Li, Hao Huang, Cheng Meng, Xiao-Ming Zhang, Lei Lv, Xiong-Wen Li, Jun Front Pharmacol Pharmacology CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For example, circCREBBP was significantly down-regulated in primary hepatic stellate cells (HSCs) and liver tissue of HF mice induced by CCl4 compared to those in the vehicle group. Overexpression of circCREBBP with AAV8-circCREBBP in vivo prevented CCl4-induced HF worsening by reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents, liver hydroxyproline levels, collagen deposition, and levels of pro-fibrosis genes and pro-inflammatory cytokines. Furthermore, in vitro function loss and function gain analysis showed that circCREBBP inhibited HSCs activation and proliferation. Mechanically, circCREBBP acts as a sponge for hsa-miR-1291 and subsequently promotes LEFTY2 expression. In conclusion, our current results reveal a novel mechanism by which circCREBBP alleviates liver fibrosis by targeting the hsa-miR-1291/LEFTY2 axis, and also suggest that circCREBBP may be a potential biomarker for heart failure. Frontiers Media S.A. 2021-11-22 /pmc/articles/PMC8648568/ /pubmed/34887753 http://dx.doi.org/10.3389/fphar.2021.741151 Text en Copyright © 2021 Yang, Hu, Bu, Li, Huang, Meng, Zhang, Lv and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yang, Ya-Ru
Hu, Shuang
Bu, Fang-Tian
Li, Hao
Huang, Cheng
Meng, Xiao-Ming
Zhang, Lei
Lv, Xiong-Wen
Li, Jun
Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis
title Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis
title_full Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis
title_fullStr Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis
title_full_unstemmed Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis
title_short Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis
title_sort circular rna crebbp suppresses hepatic fibrosis via targeting the hsa-mir-1291/lefty2 axis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648568/
https://www.ncbi.nlm.nih.gov/pubmed/34887753
http://dx.doi.org/10.3389/fphar.2021.741151
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