Theranostics 2020; 10(11):4851-4870. doi:10.7150/thno.42423 This issue

Research Paper

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

Xin Chen1,2,3*, Hai-Di Li1,2,3*, Fang-Tian Bu1,2,3*, Xiao-Feng Li1,2*, Yu Chen1, Sai Zhu1,2, Jia-Nan Wang1, Si-Yu Chen1,3, Ying-Yin Sun1,2, Xue-Yin Pan1,3, Na-Na Yin1, Jie-Jie Xu2, Cheng Huang1,2,3, Jun Li1,2,3✉

1. School of Pharmacy, Anhui Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China.
2. The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei 230032, China.
3. Institute for Liver Diseases of Anhui Medical University, ILD-AMU, Anhui Medical University, Hefei 230032, China.
*These authors contributed equally to this work.

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Citation:
Chen X, Li HD, Bu FT, Li XF, Chen Y, Zhu S, Wang JN, Chen SY, Sun YY, Pan XY, Yin NN, Xu JJ, Huang C, Li J. Circular RNA circFBXW4 suppresses hepatic fibrosis via targeting the miR-18b-3p/FBXW7 axis. Theranostics 2020; 10(11):4851-4870. doi:10.7150/thno.42423. Available from https://www.thno.org/v10p4851.htm

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Abstract

Graphic abstract

Rationale: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: hepatic fibrosis, circular RNAs, circFBXW4, miR-18b-3p, FBXW7