MEX3A Promotes The Proliferation And Metastasis Of Lung Cancer By Binding To MST1 To Regulate The Activity Of The Hippo Pathway

Background:High morbidity and mortality contribute lung cancer to become one of the most severe malignancies in the world.Although treatment consisted of surgery and radiochemotherapy make great improvement,long-term prognosis for lung cancer patients remains poor.MEX3A was first described in C.elegans,which correlated with tumor formation and promote cell proliferation and tumor metastasis.Link of MEX3A and lung cancer is still unclear so far,whether MEX3A could serve as biological marker and a new target of lung cancer is the key for our investigation.Methods:Expression of MEX3A in lung cancer and adjacent normal tissues was detected by database,immunohistochemistry and western blot,we then analysis the correlation with clinicopathological factors.The effects of MEX3A gene expression level on the malignant phenotypes of lung cancer cells was verified in vitro.The activity of Hippo pathway were observed through dual-luciferase assay,nuclear and cytoplasmic extraction and western blot.Immunofluorescence and immunoprecipitation was used to improvement the potential target in Hippo pathway.Results:1.GEPIA and Kaplan-Merier databases suggested that Mex3A was highly expressed in lung cancer tissues and was associated with poor prognosis.Immunohistochemical results revealed that Mex3A was positively expressed in lung cancer tissues,and its high expression was positively correlated with low differentiation degree,high TNM stage and lymph node metastasis of lung cancer.2.The expression of Mex3A was bidirectional regulated by plasmid and si RNA in vitro,and it was found that the transfection of Mex3A could promote the proliferation and invasion of lung cancer cells,and the levels of proliferation and EMT-related mesenchymal phenotypic proteins were increased.3.Dual luciferase reporter gene and Western blot results showed that Mex3A could inhibit Hippo pathway activity,while immunofluorescence and nucleoplasmic protein isolate experiments showed that Mex3A could promote nuclear translocation of YAP.Further research has shown that this works by binding to MST1.Conclusion:MEX3A is highly expressed in NSCLC and is one of the influencing factors for poor prognosis in NSCLC patients.MEX3A promotes malignant phenotype of lung cancer cells by binding with MST1 to inhibit HIPOO pathway activity.