Ubiquitin-like modifier activating enzyme 2 promotes cell migration and invasion through Wnt/β-catenin signaling in gastric cancer
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 prolif...
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Published in | World journal of gastroenterology : WJG Vol. 24; no. 42; pp. 4773 - 4786 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Baishideng Publishing Group Inc
14.11.2018
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Abstract | 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 (
< 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. |
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AbstractList | 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. 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 ( < 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. |
Author | Meng, Xiang-Wei Liu, Wan-Qi Sun, Xun Zou, Ya-Bin He, Ping Li, Ji Wang, Quan |
Author_xml | – sequence: 1 givenname: Ji surname: Li fullname: Li, Ji organization: Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China – sequence: 2 givenname: Xun surname: Sun fullname: Sun, Xun organization: Department of Pathology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China – sequence: 3 givenname: Ping surname: He fullname: He, Ping organization: Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China – sequence: 4 givenname: Wan-Qi surname: Liu fullname: Liu, Wan-Qi organization: Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China – sequence: 5 givenname: Ya-Bin surname: Zou fullname: Zou, Ya-Bin organization: Department of Pathology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China – sequence: 6 givenname: Quan surname: Wang fullname: Wang, Quan organization: Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China – sequence: 7 givenname: Xiang-Wei surname: Meng fullname: Meng, Xiang-Wei email: mengxw@jlu.edu.cn organization: Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China. mengxw@jlu.edu.cn |
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Keywords | Epithelial-mesenchymal transition Ubiquitin-like modifier activating enzyme 2 Wnt/β-catenin signaling pathway Gastric cancer |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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. Telephone: +86-431-85619183 Fax: +86-431-85619183 Supported by the Science and Technology Department of Jilin Province (No. 20150204006YY). 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. mengxw@jlu.edu.cn |
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Snippet | To investigate the function and mechanism of ubiquitin-like modifier activating enzyme 2 (Uba2) in progression of gastric cancer (GC) cells.
Uba2 level in... AIMTo investigate the function and mechanism of ubiquitin-like modifier activating enzyme 2 (Uba2) in progression of gastric cancer (GC) cells.METHODSUba2... |
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SubjectTerms | Basic Study Cell Line, Tumor Cell Movement Cell Proliferation - genetics Disease Progression Epithelial-Mesenchymal Transition Female Gene Knockdown Techniques Humans Male Middle Aged Neoplasm Invasiveness - pathology Stomach - pathology Stomach Neoplasms - pathology Ubiquitin-Activating Enzymes - metabolism Up-Regulation Wnt Signaling Pathway |
Title | Ubiquitin-like modifier activating enzyme 2 promotes cell migration and invasion through Wnt/β-catenin signaling in gastric cancer |
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