Overexpression Of MYC Binding Protein Promotes Invasion And Migration In Gastric Cancer

Background:Gastric cancer(GC)is the second leading cause of cancer-associated mortality worldwide.Although the mortality rate of patients with GC has improved,it remains a significant health issue.The MYC proto-oncogene protein serves key roles in cellular proliferation,differentiation,transformation and apoptosis.Previous studies have identified the abnormal expression of MYC-binding protein(MYCBP)during tumorigenesis in multiple types of cancer.Furthermore,evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types,including colon cancer and glioma;however,its influence on GC remains unclear.In the present study,the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction.Additionally,GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1(LEF-1)and assessed by in vitro Transwell migration and invasion assays.The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues,respectively.Furthermore,MYCBP downregulation notably inhibited the metastatic capacity of GC cells,and LEF-1 knockdown was found to downregulate the expression of MYCBP.On the basis of the findings of the present study,MYCBP may be a direct target of the β-catenin/LEF-1 pathway via binding LEF-1,and could potentially be used as a biomarker for the diagnosis and prognosis of GC.Objective: To investigate the MYCBP expression in gastric cancer tissue and cells.To investigate the role of MYCBP in the development and progression of GC by using Transwell assays and Western Blot and to provide the basis for early diagnosis and prognosis of tumor.Methods: A total of 77 fresh specimens from patients via GC resection without radiotherapy and chemotherapy before surgery were acquired from Zhejiang Provincial People’s Hospital between January and December 2015.Paired adjacent non-cancerous tissues were also obtained from patients.Analysis of MYCBP expression in gastric cancer,as well as the specific molecular mechanism of action by using siRNA transfection,real time quantitative PCR detection and Western blot analysis(total protein extraction),tumor cell migration and invasion experiment,cell cycle and apoptosis with SGC-7901、MKN-45、AGS and BGC-823.Results: The expression level of MYCBP in gastric cancer tissue was significantly increased compared to that of paired adjacent non-cancerous tissues.The expression level of MYCBP in gastric cancer cell line was higher than that of human gastric mucosal epithelial GES-1 cell line.Moreover,the down-regulation of the expression level of MYCBP or LEF-1 can inhibit the invasion and migration of gastric cancer cells,and can block the cell cycle in G1 phase.There is a positive regulation relationship between MYCBP and LEF-1 by Western Blot.Conclusion: MYCBP plays a role of oncogene in gastric cancer,and MYCBP is a downstream gene of LEF-1 of the Wnt signaling pathway in gastric cancer.