Biological Effect And Mechanism Of NF45 In Esophageal Squamous Cell Carcinoma

OBJECTIVE: Esophageal cancer is a tumor with a high mortality rate worldwide.The pathological types of esophageal cancer can be divided into esophageal squamous cell carcinoma and adenocarcinoma.Most patients have had invasion and metastasis when they have confirmed esophageal cancer.Understanding the invasion mechanism of esophageal squamous cell carcinoma is a key factor in the treatment of esophageal cancer.NF45 is a double-stranded RNA-binding protein that promotes the invasion of a variety of tumor cells.However,the role and mechanism of NF45 in esophageal squamous cell carcinoma has not been reported in the literature.METHODS: The expression of NF45 in esophageal squamous cell carcinoma was analyzed by immunohistochemistry and RT-PCR.The expression of NF45 was correlated with clinicopathological parameters.The silencing/overexpression of NF45 lentiviral plasmid was constructed and transferred.ECA109 and KYSE180 cells were stained with Western blot to detect the silencing/overexpression effects of NF45,and biological function of NF45 in esophageal squamous cell carcinoma cell lines was studied by MTT assay,colony formation assay,Transwell chamber invasion assay,scratch assay,and mice subcutaneous tumor formation model;construction of 14-3-3?-sh RNA lentiviral plasmid and transfection of KYSE180 cells,detection of changes in Tiam1-Rac1 pathway activity by Rac1 G15 A pulldown,PAK PBD pulldown assay to study 14-3-3? role and the role of NF45 in the invasion of esophageal squamous cell carcinoma.RESULTS: Our results showed that NF45 was significantly increased in esophageal squamous cell carcinoma compared with normal peritumoral tissues and was closely related to tumor invasion;cell functional studies showed that silencing NF45 inhibited the proliferation and invasion of esophageal squamous cell carcinoma,overexpression of NF45 can promote the proliferation and invasion of esophageal squamous cell carcinoma;the expression of 14-3-3? is related to NF45,and the silencing of 14-3-3? can counteract the overexpression of NF45.The resulting tumor-inducing effect,NF45 activates the downstream Tiam1/Rac1 pathway via 14-3-3?.CONCLUSION: The above experimental results show that NF45 promotes the invasion and proliferation of esophageal squamous cell carcinoma by promoting the expression of 14-3-3? and activating the downstream Tiam1/Rac1 pathway.This study provides a new idea for the molecular mechanism and clinical treatment of esophageal squamous cell carcinoma,and targeted regulation of NF45 is expected to become a treatment for esophageal squamous cell carcinoma.