Study On Hippo Signaling Pathway Induced By Low Expression Of MiR-378d In Polyploid Esophageal Squamous Cell Carcinoma

Objective:To investigate the relationship between tumor YAP expression level in patients with esophageal squamous cell carcinoma(ESCC)and their clinicopathological features and prognosis,as well as the molecular mechanism of polyploid tumor cell formation.Methods:Through gene chip screening and ploidy analysis of esophageal squamous cell carcinoma polyploid tumor cells,the strong correlation between miR-378d molecule and polyploid tumor cells was detected Western Blot and IHC methods were used to detect the expression levels of related molecules in the Hippo signaling pathway after the silencing of miR-378d.The relationship between miR-378d molecule and Hippo signaling pathway was further verified by nude mouse liver transplantation tumor model.To analyze the relationship between the clinicopathological features and prognosis of patients with ESCC and the expression level of YAP.Results:1.Through gene chip screening and ploidy analysis of esophageal polyploid tumor cells,it was found that the miR-378d molecule was closely related to the formation of polyploid tumor cells in ESCC.Western Blot analysis showed that after miR-378d was inhibited,the expression of YAP/TAZ,an effector of Hippo signaling pathway,was increased,and the entry of YAP/TAZ into the nucleus was increased.while the cytoplasmic p-YAP was decreased.At the same time,the expression of p53 protein also decreased,and the formation of polyploid tumor cells mainly played its role through the miR-378d-Hippo-p53 signaling pathway.2.The silencing of miR-378d promoted peritoneal metastasis of xenograft tumors in nude mice,and a large number of polyploid tumor cells appeared,while death occurred in mice.3.Statistical analysis of the relationship between YAP expression level and the clinicopathological features and prognosis of patients with E SCC showed that patients with co-expression of YAP protein in the nucleus and cytoplasm had a good prognosis,patients with high expression of YAP in the cytoplasm had a good prognosis,and patients with high expression of YAP in the nucleus had a poor prognosis.Conclusion:The low expression of miR-378d promotes the generation of esophageal squamous cell carcinoma polyploid tumor cells through Hippo-p53 pathway.Patients with co-expression of YAP protein in the nucleus and cytoplasm had a good prognosis,patients with high expression of YAP in the cytoplasm had a good prognosis,and patients with high expression of YAP in the nucleus had a poor prognosis.