Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2020; 26(35): 5328-5342
Published online Sep 21, 2020. doi: 10.3748/wjg.v26.i35.5328
RBBP4 promotes colon cancer malignant progression via regulating Wnt/β-catenin pathway
Yan-Dong Li, Zhen Lv, Wei-Fang Zhu
Yan-Dong Li, Division of Colon and Rectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Zhen Lv, Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Wei-Fang Zhu, Division of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Author contributions: Li YD designed, supervised the study and provided consultation during the entire study; Lv Z performed the research; Zhu WF analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Supported by Zhejiang Provincial Natural Science Foundation of China, No. LQ18H160011 and No. LY20H030011.
Institutional review board statement: The study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University Institutional Review Board, No. 2019-290.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Wfzhu@163.com. Participants gave informed consent for data sharing.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Wei-Fang Zhu, MD, Assistant Professor, Division of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. wfzhu@163.com
Received: July 6, 2020
Peer-review started: July 6, 2020
First decision: July 28, 2020
Revised: August 7, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: September 21, 2020
Processing time: 73 Days and 1.4 Hours
Abstract
BACKGROUND

Our previous study demonstrated that RBBP4 was upregulated in colon cancer and correlated with poor prognosis of colon cancer and hepatic metastasis. However, the potential biological function of RBBP4 in colon cancer is still unknown.

AIM

To investigate the biological role and the potential mechanisms of RBBP4 in colon cancer progression.

METHODS

Real-time polymerase chain reaction and western blot analysis were used to detect the expression of RBBP4 in colon cancer cell lines. The cell proliferation and viability of SW620 and HCT116 cells with RBBP4 knockdown was detected by Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine staining. The transwell assay was used to detect the invasion and migration capabilities of colon cancer cells with RBBP4 knockdown. Flow cytometry apoptosis assay was used to detect the apoptosis of colon cancer cells. Western blotting analysis was used to detect the expression of epithelial-mesenchymal transition and apoptosis related markers in colon cancer. The nuclear translocation of β-catenin was examined by Western blotting analysis in colon cancer cells with RBBP4 knockdown. The TOPFlash luciferase assay was used to detect the effect of RBBP4 on Wnt/β-catenin activation. The rescue experiments were performed in colon cancer cells treated with Wnt/β-catenin activator LiCl and RBBP4 knockdown.

RESULTS

We found that RBBP4 was highly expressed in colon cancer cell lines. The 5-ethynyl-2’-deoxyuridine assay showed that knockdown of RBBP4 significantly inhibited cell proliferation. RBBP4 inhibition reduced cell invasion and migration via regulating proteins related to epithelial-mesenchymal transition. Knockdown of RBBP4 significantly inhibited survivin-mediated apoptosis. Mechanistically, the TOPFlash assay showed that RBBP4 knockdown increased activity of the Wnt/β-catenin pathway. Meanwhile, RBBP4 knockdown suppressed nuclear translocation of β-catenin. With Wnt/β-catenin activator, rescue experiments suggested that the role of RBBP4 in colon cancer progression was dependent on Wnt/β-catenin pathway.

CONCLUSION

RBBP4 promotes colon cancer development via increasing activity of the Wnt/β-catenin pathway. RBBP4 may serve as a novel therapeutic target in colon cancer.

Keywords: Colon cancer; Wnt/β-catenin; RBBP4; Epithelial-mesenchymal transition; Apoptosis; Invasion

Core Tip: Our previous study demonstrated upregulation of RBBP4 in colon cancer and correlation of poor prognosis with colon cancer and hepatic metastasis. This study explored the potential biological function of RBBP4 in colon cancer. We found that RBBP4 was highly expressed in colon cancer cell lines. Knockdown of RBBP4 significantly inhibited cell proliferation and survivin-mediated apoptosis and suppressed nuclear translocation of β-catenin. RBBP4 inhibition reduced cell invasion and migration via regulating proteins related to epithelial–mesenchymal transition. Mechanistically, RBBP4 knockdown increased activity of the Wnt/β-catenin pathway. RBBP4 may serve as a novel therapeutic target in colon cancer.