Published online Nov 14, 2018. doi: 10.3748/wjg.v24.i42.4773
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.
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.