Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2018; 24(42): 4773-4786
Published online Nov 14, 2018. doi: 10.3748/wjg.v24.i42.4773
Ubiquitin-like modifier activating enzyme 2 promotes cell migration and invasion through Wnt/β-catenin signaling in gastric cancer
Ji Li, Xun Sun, Ping He, Wan-Qi Liu, Ya-Bin Zou, Quan Wang, Xiang-Wei Meng
Ji Li, Ping He, Wan-Qi Liu, Xiang-Wei Meng, Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Xun Sun, Ya-Bin Zou, Department of Pathology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Quan Wang, Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Meng XW designed and coordinated the research; Li J performed the majority of experiments and wrote the paper; Sun X and Zou YB performed the immunohistochemistry; He P and Liu WQ analyzed the data; Wang Q performed the Western blot of the tissues.
Supported by the Science and Technology Department of Jilin Province (No. 20150204006YY).
Institutional review board statement: This study was approved by the ethics committee of The First Hospital of Jilin University.
Conflict-of-interest statement: No potential conflicts of interest were disclosed.
Data sharing statement: Data are available from the first author at
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 which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Correspondence to: Xiang-Wei Meng, MD, Chief Doctor, Professor, Department of Gastroenterology, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, Jilin Province, China.
Telephone: +86-431-85619183 Fax: +86-431-85619183
Received: August 7, 2018
Peer-review started: August 8, 2018
First decision: August 24, 2018
Revised: September 3, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: November 14, 2018

To investigate the function and mechanism of ubiquitin-like modifier activating enzyme 2 (Uba2) in progression of gastric cancer (GC) cells.


Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell proliferation. Flow cytometry was used for cell cycle analysis. Wound healing and Transwell assays were conducted to examine the effects of Uba2 on migration and invasion. Expression levels of cell cycle-related proteins, epithelial-mesenchymal transition (EMT) biomarkers, and involvement of the Wnt/β-catenin pathway was assessed by Western blotting. Activation of the Wnt/β-catenin pathway was confirmed by luciferase assay.


Uba2 expression was higher in GC than in normal tissues. Increased Uba2 expression was correlated with tissue differentiation, Lauren’s classification, vascular invasion, and TNM stage, as determined by the analysis of 100 GC cases (P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while up-regulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/β-catenin signaling pathway as a possible modulator of Uba2 oncogenic functions.


Uba2 plays a vital role in GC cell migration and invasion, possibly by regulating the Wnt/β-catenin signaling pathway and EMT.

Keywords: Ubiquitin-like modifier activating enzyme 2, Gastric cancer, Epithelial-mesenchymal transition, Wnt/β-catenin signaling pathway

Core tip: This study elucidated the function and mechanism of action of ubiquitin-like modifier activating enzyme 2 (Uba2) in gastric cancer (GC) progression. Uba2 was knocked-down or over-expressed to examine its effects on proliferation, migration and invasion of GC cells. The effects of Uba2 on the Wnt/β-catenin pathway was investigated by Western blotting and luciferase reporter assay. Uba2 affected GC cell invasion and migration by modulating the Wnt/β-catenin signaling pathway, as well as epithelial-mesenchymal transition. This study was intended to create a preclinical basis to establish Uba2 as a new molecular drug target for GC.