Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2022; 14(12): 2313-2328
Published online Dec 15, 2022. doi: 10.4251/wjgo.v14.i12.2313
N-myc downstream regulated gene 1 inhibition of tumor progression in Caco2 cells
Yi-Xiao He, Hong Shen, Yu-Zhu Ji, Hai-Rong Hua, Yu Zhu, Xiang-Fei Zeng, Fang Wang, Kai-Xin Wang
Yi-Xiao He, Yu-Zhu Ji, Department of Pathology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
Yi-Xiao He, Hai-Rong Hua, Fang Wang, Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, Yunnan Province, China
Hong Shen, Department of Pathology, Zhaotong First People’s Hospital, Zhaotong 657000, Yunnan Province, China
Yu Zhu, School of Nursing, Henan Vocational College of Applied Technology, Kaifeng 450000, Henan Province, China
Xiang-Fei Zeng, Department of Clinical Pathology, West China Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
Kai-Xin Wang, Department of Pathology, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen 518052, Guangdong Province, China
Author contributions: He YX, Shen H and Ji YZ have contributed equally to the work; He YX, Shen H and Ji YZ performed the experiments, analyzed the data and wrote the manuscript; Hua HR and Zhu Y contributed analysis tools, acquired and analyzed data; Zeng XF helped perform the analysis with constructive discussions; Wang F and Wang KX conceived and designed the experiments as well as an acquired research grant; and all authors read and approved the final version of the article.
Supported by the National Natural Science Foundation of China, No. 81260361; and Incubation Project of Mianyang Central Hospital, No. 2020FH05.
Conflict-of-interest statement: He YX, Shen H, Ji YZ, Zhu Y, Zeng XF and Wang KX were previously postgraduate students at Kunming Medical University. Wang Fang was a teacher at Kunming Medical University. All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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: Kai-Xin Wang, MD, Associate Chief Physician, Department of Pathology, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), No. 89 Taoyuan Road, Nanshan District, Shenzhen 518052, Guangdong Province, China. 313683968@qq.com
Received: July 14, 2022
Peer-review started: July 14, 2022
First decision: September 26, 2022
Revised: October 17, 2022
Accepted: November 22, 2022
Article in press: November 22, 2022
Published online: December 15, 2022
Abstract
BACKGROUND

Invasion and migration are the irreversible stages of colorectal cancer (CRC). The key is to find a sensitive, reliable molecular marker that can predict the migration of CRC at an early stage. N-myc downstream regulated gene 1 (NDRG1) is a multifunctional gene that has been tentatively reported to have a strong relationship with tumor invasion and migration, however the current molecular role of NDRG1 in CRC remains unknown.

AIM

To explore the role of NDRG1 in the development of CRC.

METHODS

NDRG1 stably over-expressed Caco2 cell line was established by lentiviral infection and NDRG1 knock-out Caco2 cell line was established by CRISPR/Cas9. Furthermore, the mRNA and protein levels of NDRG1 in Caco2 cells after NDRG1 over-expression and knockout were detected by real-time polymerase chain reaction and western blot. The cell proliferation rate was measured by the cell counting kit-8 method; cell cycle and apoptosis were detected by flow cytometry; invasion and migration ability were detected by the 24-transwell method.

RESULTS

NDRG1 over-expression inhibited Caco2 proliferation and the cell cycle could be arrested at the G1/S phase when NDRG1 was over-expressed, while the number of cells in the G2 phase was significantly increased when NDRG1 was knocked out. This suggests that NDRG1 inhibited the proliferation of Caco2 cells by arresting the cell cycle in the G1/S phase. Our data also demonstrated that NDRG1 promotes early cell apoptosis. Invasion and migration of cells were extensively inhibited when NDRG1 was over-expressed.

CONCLUSION

NDRG1 inhibits tumor progression in Caco2 cells which may represent a potential novel therapeutic strategy for the treatment of CRC.

Keywords: N-myc downstream regulated gene 1, Caco2, Colorectal cancer, Tumor progression, CRISPR/Cas9, Lentivirus infection

Core Tip: This study investigated the molecular functions of N-myc downstream regulated gene 1 (NDRG1) in the process of colorectal cancer (CRC) migration through stable over-expression or knockout of NDRG1 in the Caco2 CRC cell line. Our results showed that NDRG1 over-expression arrested the cell cycle at the G1/S phase, while its knock-out significantly increased the number of G2 phase cells. Altogether, our results highlight the fact that NDRG1 inhibits tumor progression in Caco2 cells which may provide a novel diagnostic or therapeutic tool in inhibiting the migration of CRC.