Ubiquitin-like modifier activating enzyme 2 promotes cell migration and invasion through Wnt/β-catenin signaling in gastric cancer

Abstract

AIMTo investigate the function and mechanism of ubiquitin-like modifier activating enzyme 2 (Uba2) in progression of gastric cancer (GC) cells.METHODSUba2 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.RESULTSUba2 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.CONCLUSIONUba2 plays a vital role in GC cell migration and invasion, possibly by regulating the Wnt/β-catenin signaling pathway and EMT.

Knockdown of AGGF1 inhibits the invasion and migration of gastric cancer via epithelial–mesenchymal transition through Wnt/β-catenin pathway

“…Accumulating evidences have revealed that the migration and invasion of GC cells can be modulated by EMT mechanism [20–22]. Thus, to investigate whether AGGF1 is related to EMT, the expression levels of epithelial and mesenchymal markers (E-cadherin, Vimentin, Snail) were examined in the MKN-45 and MGC-803 cells with or without AGGF1 knockdown.…”

“…Wnt/β-catenin signaling is one of the major pathways involved in EMT in the development and progression of many kinds of malignancies [22–25]. Previously, Major et al [13] have found that AGGF1 associated with and regulated 40% of Wnt/β-catenin target genes and further raised the possibility that AGGF1 functionally contributed to Wnt/β-catenin signaling in colon cancer by integrative molecular screening.…”

UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells

“…UBA2 is known to promote cell proliferation. Inhibition of UBA2 expression reduces the proliferation of colorectal cancer and gastric cancer cells regulating cyclinB1, B cell lymphoma-2, and E3 ubiquitin-protein ligase MDM2 [51,52]. Moreover, UBA2 has functions such as molecular adhesion, movement, and migration [53].…”

UBA2 Activates Wnt/β-catenin Signaling Pathway during Protection of R28 Retinal Precursor Cells from Hypoxia by Extracellular Vesicles derived from Placental Mesenchymal Stem Cells

“…UBA2 is known to promote cell proliferation. Inhibition of UBA2 expression reduces the proliferation of colorectal cancer and gastric cancer cells regulating cyclinB1, B-cell lymphoma-2, and E3 ubiquitinprotein ligase MDM2 [44,45]. Morever, UBA2 has functions such as molecular adhesion, movement and migration.…”