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World J Gastroenterol. Mar 7, 2023; 29(9): 1446-1459
Published online Mar 7, 2023. doi: 10.3748/wjg.v29.i9.1446
Role of noncoding RNAs in liver fibrosis
Qing-Yuan Li, Tao Gong, Yi-Ke Huang, Lan Kang, Charlotte A Warner, He Xie, Li-Min Chen, Xiao-Qiong Duan
Qing-Yuan Li, Tao Gong, Department of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Yi-Ke Huang, Lan Kang, Li-Min Chen, Xiao-Qiong Duan, Center for Transfusion-transmitted Infectious Diseases, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, Sichuan Province, China
Charlotte A Warner, Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
He Xie, Li-Min Chen, Department of Clinical Laboratory, The Hospital of Xidian Group, Xi’an 710077, Shaanxi Province, China
Author contributions: Gong T and Xie H collected the references; Li QY drafted the initial manuscript; Huang YK and Kang L drew the figure and tables; Chen LM and Duan XQ reviewed and revised the initial draft; Warner CA polished the language; all authors contributed to the manuscript and approved the submitted version; Chen LM and Duan XQ contributed equally to this manuscript.
Supported by Science and Technology Innovation Talent Project of Sichuan Province, No. 2022JDRC0047; the Central Government-directed Special Funds for Local Science and Technology Development Project, No. 2021ZYD0085; Natural Science Foundation of China, No. 82102383; and Qin Chuangyuan Recruited High-level Innovation and Entrepreneurship Talents Project of Science and Technology Department of Shaanxi Province, No. QCYRCXM-2022-56.
Conflict-of-interest statement: There is no conflict of interest associated with any of authors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Qiong Duan, PhD, Associate Professor, Center for Transfusion-transmitted Infectious Diseases, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 26 Huacai Road, Chengdu 610052, Sichuan Province, China. xiaoqiongduan@163.com
Received: October 4, 2022
Peer-review started: October 4, 2022
First decision: October 17, 2022
Revised: October 27, 2022
Accepted: February 27, 2023
Article in press: February 27, 2023
Published online: March 7, 2023
Abstract

Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection, obesity, or excessive alcohol. It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix. Advanced fibrosis could lead to cirrhosis and even liver cancer, which has become a significant health burden worldwide. Many studies have revealed that noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular RNAs, are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-β pathway, phosphatidylinositol 3-kinase/protein kinase B pathway, and Wnt/β-catenin pathway. NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis. NcRNAs mimics, ncRNAs in mesenchymal stem cell-derived exosomes, and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis. In this review, we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis, and discuss the potentials and challenges to use these ncRNAs for diagnosis, staging and treatment of liver fibrosis. All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.

Keywords: MicroRNAs, Long noncoding RNAs, Circular RNAs, Liver fibrosis, Diagnosis, Treatment

Core Tip: Liver fibrosis is an inevitable stage in the development of various chronic liver diseases, and manifests as an imbalance between the formation and degradation of extracellular matrix. The key mechanism of liver fibrosis is the activation of hepatic stellate cells, which is coordinately regulated by a variety of cytokines, inflammatory factors and chemokines involved in multiple cells signaling pathways. In this review, we discuss the role of noncoding RNAs (ncRNAs) in regulating the signaling pathways in the formation and regression of liver fibrosis, and the limitations, challenges, and prospects of ncRNAs in the diagnosis and treatment of liver fibrosis.