The Molecular Mechanism Of MiR-378d-AKT-?-catenin Signaling Pathway In Regulating Malignant Phenotype Of Esophageal Squamous Cell Carcinoma

Objective: miR-378 d was the most significantly differentially expressed molecule screened by the research group through paclitaxel treatment of esophageal squamous cell carcinoma cells in the early stage.This study will elucidate the molecular mechanism of miR-378 d inhibiting the malignant phenotype of esophageal squamous cell carcinoma,and the relationship between the expression level of mir-378 d and the prognosis of esophageal squamous cell carcinoma.Methods: By sequencing and bioinformatics analysis,we screened the miRNA differentially expressed by paclitaxel treated esophageal squamous cell carcinoma cell,and found the most significant molecular mir-378d;the expression level of miR-378 d was detected by in situ hybridization,and the expression of miR-378 d in esophageal cancer was analyzed Relationship with clinicopathological characteristics;construct lentivirus-infected ESCC cell lines stably overexpressing miR-378d-nc,mimics and inhibitor,and treat with different concentrations of cisplatin or 5-Fu to confirm miR-378 d enhanced chemotherapy Sensitivity;verified that miR-378 d directly targets and regulates AKT1 by Western Blot and RT-qPCR and luciferase reporter vector;confirmed that miR-378 d inhibits ESCC malignancy by regulating AKT-?-catenin signaling pathway by Western Blot and RT-qPCR Phenotype.Results: The level of miR-378 d in Esophageal squamous cellcarcinoma was significantly lower than that in normal subjects,and the patients with high miR-378 d expression had better prognosis.When miR-378 d was significantly down-regulated,esophageal squamous cell carcinoma cells underwent epithelial-mesenchymal transformation.miR-378 d enhanced Chemosensitivity,Transwell invasion assay showed that miR-378 d decreased tumor migration and invasion ability,and monoclonal assay showed miR-378 d decreased clone formation ability,Western blot and immunohistochemical results showed that miR-378 d enhanced chemosensitivity and inhibited tumor invasion by regulating AKT-?-catenin signaling pathway.Conclusion: miR-378 d regulates the AKT-?-catenin signaling pathway by targeting AKT,promotes chemotherapeutic sensitivity of esophageal squamous carcinoma cells,inhibits clonal formation,inhibits EMT and invasion and migration.Patients with high expression of miR-378 d have a good prognosis.