Jiangning Li1, Yang Zheng2, Xiaofeng Li3, Xue Dong4, Weiyan Chen5, Zhongying Guan6, Chong Zhang7. 1. Department of Laboratory Medicine, The First People's Hospital of Shenyang Shenyang, Liaoning, P. R. China. 2. Department of Laboratory Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute Shenyang, Liaoning, P. R. China. 3. Institute of Transfusion Medicine, Liaoning Blood Center Shenyang, Liaoning, P. R. China. 4. Microbiological Laboratory Center, Shenyang Center for Disease Control and Prevention Shenyang, Liaoning, P. R. China. 5. Department of Pathology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Shenyang, Liaoning, P. R. China. 6. Department of Laboratory Medicine, The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Shenyang, Liaoning, P. R. China. 7. Department of Plastic Surgery, Beijing Weiyan Medical Cosmetology Clinic Beijing, P. R. China.
Abstract
OBJECTIVE: The dysregulation of deubiquitinating enzymes is important in the development of many cancers, including colorectal cancer (CRC). However, the precise function and potential mode of action of the deubiquitinating enzyme UCHL3 in CRC progression are poorly elucidated. METHODS: The expression levels of UCHL3 in patient samples were analyzed by western blotting, real-time PCR and immunohistochemistry and its association with overall survival was analyzed using Kaplan-Meier method. Colony formation, CCK-8 and Transwell were used to examine the effects of UCHL3 knockdown or over-expression on CRC cells growth, invasion and migration. The functional effects of UCHL3 and SOX12 on tumor growth were further examined using xenograft tumor mouse models in vivo. RESULTS: Here, we found high expression of UCHL3 in CRC tissues which showed an association with the development of tumor and CRC patient survival. Studies conducted in vitro showed that UCHL3 overexpression facilitates proliferation, invasion, migration, and EMT (epithelial-mesenchymal transition) in cells of CRC, and a knockdown of UCHL3 had a reverse effect. Likewise, experiments conducted in vivo also showed enhanced tumor growth due to UCHL3 overexpression. In addition, UCHL3 was found regulates SOX12 expression in CRC cells. PI3K/AKT/mTOR pathway is required for UCHL3-mediated SOX12 expression. Mechanically, UCHL3 regulates SOX12 via AKT/mTOR signaling pathway and facilitated tumor progression. CONCLUSION: UCHL3 plays an oncogenic role through the AKT/mTOR/SOX12 axis and can be considered as a potential target for therapy and CRC prognostic biomarker. AJTR
OBJECTIVE: The dysregulation of deubiquitinating enzymes is important in the development of many cancers, including colorectal cancer (CRC). However, the precise function and potential mode of action of the deubiquitinating enzyme UCHL3 in CRC progression are poorly elucidated. METHODS: The expression levels of UCHL3 in patient samples were analyzed by western blotting, real-time PCR and immunohistochemistry and its association with overall survival was analyzed using Kaplan-Meier method. Colony formation, CCK-8 and Transwell were used to examine the effects of UCHL3 knockdown or over-expression on CRC cells growth, invasion and migration. The functional effects of UCHL3 and SOX12 on tumor growth were further examined using xenograft tumormouse models in vivo. RESULTS: Here, we found high expression of UCHL3 in CRC tissues which showed an association with the development of tumor and CRC patient survival. Studies conducted in vitro showed that UCHL3 overexpression facilitates proliferation, invasion, migration, and EMT (epithelial-mesenchymal transition) in cells of CRC, and a knockdown of UCHL3 had a reverse effect. Likewise, experiments conducted in vivo also showed enhanced tumor growth due to UCHL3 overexpression. In addition, UCHL3 was found regulates SOX12 expression in CRC cells. PI3K/AKT/mTOR pathway is required for UCHL3-mediated SOX12 expression. Mechanically, UCHL3 regulates SOX12 via AKT/mTOR signaling pathway and facilitated tumor progression. CONCLUSION:UCHL3 plays an oncogenic role through the AKT/mTOR/SOX12 axis and can be considered as a potential target for therapy and CRC prognostic biomarker. AJTR
Authors: Lei Wang; Fengqing Hu; Saie Shen; Haibo Xiao; Guoqing Li; Mingsong Wang; Ju Mei Journal: Am J Transl Res Date: 2017-09-15 Impact factor: 4.060
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