OncoTargets and Therapy (Nov 2020)
The Effects of TRAF6 on Growth and Progression in Colorectal Cancer are Regulated by miRNA-140
Abstract
Guangwei Zhu,1,* Zhibin Cheng,1,2,* Chunlin Lin,1 Qin Wang,1,2 Yongjian Huang,1 Wei Zheng,1 Shugang Yang,1 Jianxin Ye1 1Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou 350005, People’s Republic of China; 2Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianxin Ye Email [email protected] and Aim: Some studies have confirmed that miRNA-140 exhibits a suppressive role in gastric cancer, Wilms’ tumor. However, the function of miRNA-140 in colorectal cancer has not been completely elucidated. The present study aims to verify TRAF6 as the targeted gene by miRNA-140 which was investigated in colorectal cancer tissues and cells, and its effects on the biological characteristics of colorectal cancer cells were determined, in order to provide an experimental and theoretical basis for the application of TRAF6 in the treatment of colorectal cancer.Methods: qPCR analyzed miRNA-140 expression levels in colorectal cancer tissues, normal colorectal cancer tissues and colorectal cells including SW480 and HCT116 cancer cells and FHC normal colorectal epithetical cells. A serial biological experiment analyzed miRNA-140 effects on cell proliferation, migration and invasion capacities in SW480 and HCT116 cells. miRNA targeting gene prediction and a dual luciferase assay were used to analyze miRNA-140-targeted TRAF6. qPCR and Western blot analyzed miRNA-140 effects on the mRNA and protein expression of TRAF6. Western blot analyzed miRNA-140 effects on NF-κB/c-jun signaling pathways. Animal studies were performed to investigate the effects of miRNA-140 on colorectal cancer implantation tumor growth. Immunohistochemistry analyzed TRAF6 expression in animal experimentation tumors.Results: miRNA-140 expression is lower in colorectal cancer tissues and colorectal cancer cells. Over-expression of miRNA-140 inhibited the proliferation, migration and invasion capacities of colorectal cancer cells. miRNA-140 targeted the TRAF6 mRNA 3ʹUTR area and decreased TRAF6 protein expression. miRNA-140 suppressed p-NF-κB/p-c-jun proteins expression. miRNA-140 inhibited colorectal cancer implantation tumor growth in the mice model.Conclusion: miRNA-140 targeting TRAF6 affects the progression and growth of colorectal cancer, the mechanism could be miRNA-140 decreasing the TRAF6 expression effects on the NF-κB/c-jun signaling pathways.Keywords: TRAF6, miRNA-140, NF-kB/c-jun signaling pathways, progression, colorectal cancer
