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:	Ya-Ru Yang, Shuang Hu, Fang-Tian Bu, Hao Li, Cheng Huang, Xiao-Ming Meng, Lei Zhang, Xiong-Wen Lv, Jun Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	biomarker HF circCREBBP miR-17-5p hsa-miR-1291 LEFTY2 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/cad8c34b551f48cd94627324afd4da69
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spelling	oai:doaj.org-article:cad8c34b551f48cd94627324afd4da692021-11-30T10:12:43ZCircular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis1663-981210.3389/fphar.2021.741151https://doaj.org/article/cad8c34b551f48cd94627324afd4da692021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.741151/fullhttps://doaj.org/toc/1663-9812CircRNAs (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.Ya-Ru YangShuang HuShuang HuFang-Tian BuFang-Tian BuHao LiHao LiCheng HuangCheng HuangXiao-Ming MengXiao-Ming MengLei ZhangLei ZhangXiong-Wen LvXiong-Wen LvJun LiJun LiFrontiers Media S.A.articlebiomarkerHFcircCREBBPmiR-17-5phsa-miR-1291LEFTY2Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	biomarker HF circCREBBP miR-17-5p hsa-miR-1291 LEFTY2 Therapeutics. Pharmacology RM1-950
spellingShingle	biomarker HF circCREBBP miR-17-5p hsa-miR-1291 LEFTY2 Therapeutics. Pharmacology RM1-950 Ya-Ru Yang Shuang Hu Shuang Hu Fang-Tian Bu Fang-Tian Bu Hao Li Hao Li Cheng Huang Cheng Huang Xiao-Ming Meng Xiao-Ming Meng Lei Zhang Lei Zhang Xiong-Wen Lv Xiong-Wen Lv Jun Li Jun Li Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis
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.
format	article
author	Ya-Ru Yang Shuang Hu Shuang Hu Fang-Tian Bu Fang-Tian Bu Hao Li Hao Li Cheng Huang Cheng Huang Xiao-Ming Meng Xiao-Ming Meng Lei Zhang Lei Zhang Xiong-Wen Lv Xiong-Wen Lv Jun Li Jun Li
author_facet	Ya-Ru Yang Shuang Hu Shuang Hu Fang-Tian Bu Fang-Tian Bu Hao Li Hao Li Cheng Huang Cheng Huang Xiao-Ming Meng Xiao-Ming Meng Lei Zhang Lei Zhang Xiong-Wen Lv Xiong-Wen Lv Jun Li Jun Li
author_sort	Ya-Ru Yang
title	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_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_sort	circular rna crebbp suppresses hepatic fibrosis via targeting the hsa-mir-1291/lefty2 axis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cad8c34b551f48cd94627324afd4da69
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Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis

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