HMGA1 Promotes Gastric Cancer Cells Invasion And Metastasis By Transactivating SUZ12 And CCDC43 Expression

Background and objection:Gastric cancer(GC)is one of the most common malignant tumors and the second leading cause of cancer deaths.The majority of GC diagnoses occur at the middle or late stage of the disease,due to lacking of physical examination awareness by patients and the low early detection and diagnosis rate of gastric cancer by doctors.Moreover,the 5-year survival rate and the prognosis of advanced-stage gastric cancer is low,indicating to explore the molecular mechanisms underlying GC invasion and metastasis is urgent.Recent studies suggested HMGA1 was berrant expression in many tumors,such as liver cancer,pancreatic cancer.However,the expression of HMGA1 and its relative regulatory mechanisms remain unclear in GC.In the current study,we found that transcription factors HMGA1 regulate the invasion and metastasis of gastric cancer cells by regulating SUZ12 and CCDC43 expression.Therefore,we will focus on four direction of the cell function,molecular interaction,animal experiments and correlation of tumor patients's samples to clarify the biological function of HMGA1 in gastric cancer and explore its regulatory mechanism,and provide a basis for finding a new potential target for diagnosis and treatment of GC.Methods:1.Use Western blot to detect the expression level of HMGA1 in gastric cancer cells and normal gastric epithelial cells.The expression level of HMGA1 in gastric cancer and adjacent tissues was detected by immunohistochemical staining,and the relationship between HMGA1 expression and clinicopathological parameters and prognosis was analyzed by chi-square inspection.Overexpress and interfere with HMGA1 in gastric cancer cells respectively,and detect the ability of HMGA1 to proliferate,invade and migrate gastric cancer cells.2.SUZ12 and CCDC43 were also significantly increased after overexpression of HMGA1.The correlation was verified by bioinformatics,and the dual luciferase reporter system and ChIP experiment were used to verify that HMGA1 is its common transcription factor.HMGA1 positively regulate the expression of SUZ12 and CCDC43 in gastric cancer cells detected by Westren blot.3.By interfering with SUZ12 and CCDC43,detect its effects of HMGA1 to promote the proliferation,invasion and migration in gastric cancer cells.4.Analyze the correlation of HMGA1/SUZ12/CCDC43 in gastric cancer tissues by Westren blot,immunohistochemistry,animal experiments.Results:1.HMGA1 was highly expressed in gastric cancer cells,and HMGA1 expression level was correlated with differentiation,lymph node metastasis,AJCC stage,tumor size and prognosis of gastric cancer;HMGA1 promotes the proliferation,invasion and metastasis of gastric cancer cells.2.HMGA1 was common transcription factor of SUZ12/CCDC43,and HMGA1 promotes the proliferation,invasion and metastasis of gastric cancer by transactivating SUZ12/CCDC43expression.3.By interfering with SUZ12 and CCDC43,it can inhibit the ability of HMGA1 to promote the proliferation,invasion and migration of gastric cancer cells4.HMGA1 and SUZ12/CCDC43 is positively correlated in gastric cancer tissueConclusions:HMGA1 was highly expressed in gastric cancer cells and promotes GC invasion and metastasis by transactivating SUZ12 and CCDC43 expression,highlighting HMGA1 as a potential prognostic biomarker in the treatment of GC.