Guangwei Zhu1, Zhibin Cheng1, Yongjian Huang2, Wei Zheng2, Shugang Yang2, Chunlin Lin2, Jianxin Ye1. 1. Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou 350005, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350000, China. 2. Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou 350005, China.
Abstract
AIMS: TRAF6 is an intracellular signal adapter molecule plays a significant role in tumor development. However, the specific mechanism causes and promotes of colorectal cancer keep largely unknown. Therefore, we sought to investigate the roles and the molecular mechanisms of TRAF6 in regulation colorectal cancer. MATERIAL AND METHODS: The immunohistochemistry analyzed the expression of TRAF6 in colorectal cancer samples and analyzed the effects of expression of TRAF6 on the prognosis in colorectal cancer. The roles of TRAF6 in regulating colorectal cancer cell proliferation, colony formation, cell migration, cell wound healing and cell invasion were evaluated in vitro. Animal studies were performed to investigate the effects of TRAF6 on tumor growth. mRNA abundance of key genes was analyzed via qPCR. Protein level of TRAF6 and NF-κB/AP-1 signaling pathways was examined by Western blot. Luciferase reporter and Immunofluorescence assays were used to identify the activities NF-κB/AP-1 signaling pathways. KEY FINDINGS: TRAF6 high expression in colorectal cancer tissues. And colorectal cancer patients with high expression of TRAF6 had a poor survival rate. TRAF6 knockdown can inhibit proliferation, migration, and invasion of colorectal cancer cells in vitro and in vivo experiments. TRAF6 activates the TRAF6-NF-κB/AP-1 signaling pathway by entering the nucleus, causing biobehavioral changes in colorectal cancer cells. SIGNIFICANCE: TRAF6 plays a vital role in the progression of colorectal cancer. What's more, research elucidating the biological mechanisms of TRAF6 can treated as potential therapeutic target for colorectal cancer.
AIMS: TRAF6 is an intracellular signal adapter molecule plays a significant role in tumor development. However, the specific mechanism causes and promotes of colorectal cancer keep largely unknown. Therefore, we sought to investigate the roles and the molecular mechanisms of TRAF6 in regulation colorectal cancer. MATERIAL AND METHODS: The immunohistochemistry analyzed the expression of TRAF6 in colorectal cancer samples and analyzed the effects of expression of TRAF6 on the prognosis in colorectal cancer. The roles of TRAF6 in regulating colorectal cancer cell proliferation, colony formation, cell migration, cell wound healing and cell invasion were evaluated in vitro. Animal studies were performed to investigate the effects of TRAF6 on tumor growth. mRNA abundance of key genes was analyzed via qPCR. Protein level of TRAF6 and NF-κB/AP-1 signaling pathways was examined by Western blot. Luciferase reporter and Immunofluorescence assays were used to identify the activities NF-κB/AP-1 signaling pathways. KEY FINDINGS:TRAF6 high expression in colorectal cancer tissues. And colorectal cancerpatients with high expression of TRAF6 had a poor survival rate. TRAF6 knockdown can inhibit proliferation, migration, and invasion of colorectal cancer cells in vitro and in vivo experiments. TRAF6 activates the TRAF6-NF-κB/AP-1 signaling pathway by entering the nucleus, causing biobehavioral changes in colorectal cancer cells. SIGNIFICANCE: TRAF6 plays a vital role in the progression of colorectal cancer. What's more, research elucidating the biological mechanisms of TRAF6 can treated as potential therapeutic target for colorectal cancer.
Authors: Zhu Guangwei; Cheng Zhibin; Wang Qin; Lin Chunlin; Lin Penghang; He Ruofan; Chen Hui; Robert M Hoffman; Ye Jianxin Journal: Cancer Sci Date: 2022-03-01 Impact factor: 6.716