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环状RNA circFBXW4通过靶向miR-18b-3p/FBXW7轴抑制肝纤维化。

Circular RNA circFBXW4 suppresses hepatic fibrosis via targeting the miR-18b-3p/FBXW7 axis.

作者信息

Chen Xin, Li Hai-Di, Bu Fang-Tian, Li Xiao-Feng, Chen Yu, Zhu Sai, Wang Jia-Nan, Chen Si-Yu, Sun Ying-Yin, Pan Xue-Yin, Yin Na-Na, Xu Jie-Jie, Huang Cheng, Li Jun

机构信息

School of Pharmacy, Anhui Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China.

The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei 230032, China.

出版信息

Theranostics. 2020 Mar 26;10(11):4851-4870. doi: 10.7150/thno.42423. eCollection 2020.

Abstract

: Circular RNAs (circRNAs) are a new form of noncoding RNAs that play crucial roles in various pathological processes. However, the expression profile and function of circRNAs in hepatic fibrosis (HF) remain largely unknown. In this study, we show a novel circFBXW4 mediates HF via targeting the miR-18b-3p/FBXW7 axis. : We investigated the expression profile of circRNAs, microRNAs and mRNAs in hepatic stellate cells (HSCs) from HF progression and regression mice by circRNAs-seq and microarray analysis. We found a significantly dysregulated circFBXW4 in HF. Loss-of-function and gain-of-function analysis of circFBXW4 were performed to assess the role of circFBXW4 in HF. Furthermore, we confirmed that circFBXW4 directly binds to miR-18b-3p by luciferase reporter assay, RNA pull down and fluorescence in situ hybridization analysis. : We found that circFBXW4 downregulated in liver fibrogenesis. Enforcing the expression of circFBXW4 inhibited HSCs activation, proliferation and induced apoptosis, attenuated mouse liver fibrogenesis injury and showed anti-inflammation effect. Mechanistically, circFBXW4 directly targeted to miR-18b-3p to regulate the expression of FBXW7 in HF. : circFBXW4 may act as a suppressor of HSCs activation and HF through the circFBXW4/miR-18b-3p/FBXW7 axis. Our findings identify that circFBXW4 serves as a potential biomarker for HF therapy.

摘要

环状RNA(circRNAs)是一种新型非编码RNA,在各种病理过程中发挥关键作用。然而,circRNAs在肝纤维化(HF)中的表达谱和功能仍 largely未知。在本研究中,我们发现一种新型circFBXW4通过靶向miR-18b-3p/FBXW7轴介导HF。

我们通过circRNAs测序和微阵列分析研究了HF进展和消退小鼠肝星状细胞(HSCs)中circRNAs、微小RNA和信使RNA的表达谱。我们发现HF中circFBXW4显著失调。对circFBXW4进行功能丧失和功能获得分析以评估circFBXW4在HF中的作用。此外,我们通过荧光素酶报告基因检测、RNA下拉和荧光原位杂交分析证实circFBXW4直接与miR-18b-3p结合。

我们发现circFBXW4在肝纤维化过程中下调。增强circFBXW4的表达可抑制HSCs活化、增殖并诱导凋亡,减轻小鼠肝纤维化损伤并显示抗炎作用。机制上,circFBXW4直接靶向miR-18b-3p以调节HF中FBXW7的表达。

circFBXW4可能通过circFBXW4/miR-18b-3p/FBXW7轴作为HSCs活化和HF的抑制剂。我们的发现确定circFBXW4作为HF治疗的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faff/7163456/a2d1d182689c/thnov10p4851g001.jpg

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