| Background&AimsColorectal cancer(CRC)is one of the most common malignant tumors in digestive tract system.Its morbidity and mortality rank third and fourth in the world,respectively,which threatens human life and health for a long time.The occurrence and metastasis of colorectal cancer is a multi-factor,multi-step and extremely complex biological process,and its molecular basis and mechanism are not fully understood,which seriously affects its treatment and prognosis.S100 calcium binding protein A16(S100A16)is a small molecule acidic Ca2 binding protein that plays an important role in tumor progression.Existing studies have confirmed that S100A16 can promote the progression of breast,prostate and pancreatic cancer,while inhibiting tumor progression in oral cancer,acute B lymphoblastic leukemia cells and suggests that the role of S100A16 in the development of different tumors is more complex.Studies have shown that S100A16 low expression in colorectal cancer suggests poor prognosis,the survival time is shorter in colorectal cancer patients with low S100A16 expression,but the role and mechanism of S100A16 in colorectal cancer is not clear.Thereolorevfore,the purpose of this project is to answer these questions:1.Whther S100A16 is low expression in colorectal cancer,how is the relationship between its expression and clinicopathological parameters;2.Whether S100A16 play a cruial role in the progression and metastasis of colorectal cancer;3.What is the possible molecular pathways and mechanisms of S100A16 in colorectal cancer.We hope this study will provide a theoretical basis for understanding the mechanism of colorectal occurrence and metastasis,which best for clinical diagnosis,treatment,prognosis judgment and possible intervention targets for CRC.Methods1.Immunohistochemical assay to evaluate the expression levels of S100A16 in 70 paired colorectal cancer tissues and adjacent normal tissues.Collect and collate the clinicopathological data of 104 patients with colorectal cancer,and analyze the correlation between S100A16 expression and clinicopathological features and survival prognosis of patients with colorectal cancer.2.Cell counting kit-8(CCK-8)?Transwell and Western blot experiments were used to evaluate the effects of S100A16 on the proliferation,migration and invasion ability of colorectal cancer cells.Construction of mouse model to observe the effect of S100A16 on subcutaneous transplanted tumor in nude mice.3.Western blot assays were used to detect the expression of MAPK signaling pathways and EMT key proteins closely related to colorectal cancer after knockdown S100A16 in colorectal cancer cells.4.The expression of MAPK pathway and EMT key proteins were detected by Western blot,the migration and invasion ability were evaluated by Transwell assays after treatment with the related pathway inhibitors in S100A16-silencing colorectal cancer cells.Results1.Immunohistochemical results showed that the expression of S100A16 in colorectal cancer tissues was lower than that of paired adjacent normal tissues(P<0.01).The statistical analysis showed that S100A16 expression was associated with tumor pathological differentiation,lymph node metastasis-And the survival time of patients with S100A16 high expression was significantly higher than that of patients with S100A16 low expression.2.Knockdown S100A16 can promote the proliferation,migration and invasion of colorectal cancer cells,and overexpression S100A16 can inhibit the proliferation,migration and invasion of colorectal cancer cells in vitro(P<0.01).Subcutaneous tumorigenesis in nude mice showed that S100A16 could inhibit the growth of subcutaneous transplanted tumors(P<0.01)3.After knock-down S100A16 in colorectal cancer cells,the phosphorylated protein of the JNK/P38 MAPK signaling pathway were significantly increased(P<0.01),E-cad expression was decreased(P<0.01),and N-cad,Vimentin expression were significantly increased(P<0.01).4.The expression of phosphorylated proteins of JNK/P38 and EMT related proteins were recovered after treatment with JNK/P38MAPK specific inhibitors in knock-down S100A16 colorectal cancer cells(P<0.01).The transwell test suggested that the migration and invasion ability of colorectal cancer cell line HCT116 after treatment with inhibitor was weaker than that of knock-down groups(P<0.01).Conclusion1.S100A16 was low expression in colorectal cancer tissue and significantly associated with poor prognosis in colorectal cancer patients.2.S100A16 inhibits proliferation,migration and invasion in colorectal cancer cells in vitro.S100A16 can inhibit mouse xenografts growth of colorectal cancer in vivo.3.S100A16 inhibits cell proliferation,migration and invasion in CRC cells in part through the JNK/P38MAPK signaling pathways mediated epithelial-mesenchymal transition. |
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