Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2022; 28(27): 3435-3454
Published online Jul 21, 2022. doi: 10.3748/wjg.v28.i27.3435
RING finger and WD repeat domain 3 regulates proliferation and metastasis through the Wnt/β-catenin signalling pathways in hepatocellular carcinoma
Ruo-Peng Liang, Xiao-Xue Zhang, Jie Zhao, Qin-Wei Lu, Rong-Tao Zhu, Wei-Jie Wang, Jian Li, Kai Bo, Chi-Xian Zhang, Yu-Ling Sun
Ruo-Peng Liang, Jie Zhao, Qin-Wei Lu, Rong-Tao Zhu, Wei-Jie Wang, Jian Li, Kai Bo, Chi-Xian Zhang, Yu-Ling Sun, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Xiao-Xue Zhang, Department of Physical Examination, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Sun YL conceived the experiments; Liang RP, Zhang XX, Zhao J, Lu QW, Zhu RT, Wang WJ, Li J, Bo K and Zhang CX contributed sample collection/reagents/materials/analysis tools, performed all experiments, and analyzed the data; Liang RP, Zhang XX and Zhao J analyzed the results and wrote the paper; all authors have read and approve the final manuscript.
Supported by National Natural Science Foundation of China, No. 82172944 and No. 81900558; Co-operation Research Plan of Medical Science and Technology of Henan Province, No. LHGJ20190149; and The Key Scientific Research Projects of Universities of Henan Province, No. 21A320052.
Institutional review board statement: This study was reviewed and approved by the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, No. 10[2017].
Institutional animal care and use committee statement: All animal experimental protocols were conducted following the ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments, https://www.nc3rs.org.uk/arrive-guidelines) and approved by Laboratory Animals and the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University (Approval Number: 10[2017]).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Yu-Ling Sun, MD, PhD, Chief Doctor, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 50 West Jianshe Road, Zhengzhou 450052, Henan Province, China. ylsun@zzu.edu.cn
Received: February 7, 2022
Peer-review started: February 7, 2022
First decision: April 5, 2022
Revised: April 16, 2022
Accepted: June 3, 2022
Article in press: June 3, 2022
Published online: July 21, 2022
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate. The molecular biology research of HCC can reveal the potential mechanism and provide direction for its comprehensive treatment.

Research motivation

The relationship between RING finger and WD repeat domain 3 (RFWD3) and the tumorigenesis process has been reported occasionally; however, the relationship between RFWD3 and HCC is still unclear.

Research objectives

We aimed to investigate the relationship between HCC and RFWD3 and explore the underlying molecular signalling transduction pathways.

Research methods

We analyzed RFWD3 expression in HCC tissues and evaluated cell phenotypes such as proliferation, apoptosis, migration, and invasion using Lentivirus mediated RFWD3 knockdown. In addition, in vivo experiments were performed to observe tumor growth and metastasis. Next, the phenotype was verified using the lentiviral-mediated rescue of RFWD3 shRNA. Finally, we unraveled the regulatory network underlying HCC using microarray, bioinformatics, and western blot analyses.

Research results

RFWD3 expression levels were correlated with tumor size and TNM stage in clinical samples. RFWD3 silencing increased apoptosis, decreased growth, and inhibited migration in HCC cell lines and nude mice, which were resumed with RFWD3 shRNAi rescue. Subsequent experiments revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.

Research conclusions

This study shows that RFWD3 affects the Wnt/β-catenin signalling pathway and therefore affects HCC tumorigenesis.

Research perspectives

The findings suggest that RFWD3 could be a potential therapeutic target for HCC. However, it warrants further investigations to ascertain these inferences.