Transcription Factor Foxd3 Inhibits Gab2 Gene Expression And Its Function On Hepatocellular Carcinoma

Liver cancer is the second leading cause of cancer death after lung cancer.Asia has become the region with the largest number of liver cancer patients in the world,and more than half of them occur in China.Current treatment methods can not completely cure liver cancer,and only sorafenib has been approved for clinical treatment in patients with liver cancer.Therefore,further elucidation of the molecular mechanism of liver cancer is very necessary to understand this disease and develop new treatment methods.Gab2,as a tumor promoting factor,provides a new idea for the development of targeted drugs for liver cancer.Gab2 is active in a variety of cancer diseases,especially as an oncogenic factor in liver cancer,Gab2 can induce the pathogenesis of hepatitis by mediating a variety of signaling molecules.In order to promote the occurrence and development of liver cancer,Gab2 can be collected by a variety of pathogenic factors to integrate multiple regulatory signals in the occurrence of liver diseases.Therefore,Gab2 may be a potential target for the treatment of liver diseases,and targeting this target may change the signaling pathway of many diseases,thus effectively reversing the trend of diseases.We started with the transcription of Gab2 gene,after analysis and screening,notice Foxd3 as a transcription factor.In contrast to Gab2,Foxd3 plays an important role in the inhibition of tumorigenesis and development in many kinds of cancer.First,EMSA assay confirmed that Foxd3 inhibits the transcription process of Gab2 gene by directly binding to the promoter region of Gab2.Next,the levels of Foxd3 and Gab2 in different layers were detected that Foxd3 was highly negatively correlated with Gab2 in liver cancer.Gab2 was significantly highly expressed in human,animal or cell,while Foxd3 was significantly low.Then,by analyzing the interaction between the two in liver cancer cells,we revealed that in liver cancer cell lines,the overexpression of Foxd3 inhibited the expression of Gab2 protein and prevented Gab2 from promoting cell proliferation,migration and tumorigenesis.Conversely,high Gab2 expression reverses the tumor suppressive effect of Foxd3,and Gab2 overexpression also inhibits Foxd3 expression in hepatocellular carcinoma.This negative feedback loop between Foxd3 and Gab2 leads to extremes in the expression of Gab2 and Foxd3 during the development of liver cancer.Finally,the absence of Gab2 has been shown to reduce Foxd3’s ability to inhibit cancer to some extent.In conclusion,tumor suppressor gene Foxd3 and tumor promoter Gab2 inhibit each other and synergistically control the occurrence of liver cancer.This study focused on the relationship between Foxd3 and Gab2 in liver cancer.The changes of two completely different acting factors in the development of liver cancer were clarified,and the functional roles of tumor suppressor Foxd3 and tumor promoting factor Gab2 were revealed,further integrating the specific effects of the two synergistic effects on liver cancer.This has laid a certain foundation for us to study effective methods to reduce Gab2 expression and develop liver cancer drugs targeting this target.