Cadherin-3(CDH3) Promotes The Growth Of Cervical Cancer Cells Through PI3K/AKT Pathway

Background and objective:Cervical carcinoma is a highly prevalent malignancy in women.Currently,its treatment consists of surgery,chemotherapy and radiotherapy,of which platinum-based drugs are often used.Although chemotherapy contributed to improve the survival rate of the patients,poor prognosis and high recurrence rate remain to be solved.The development of cervical cancer may be closely related to a variety of cytokines and gene regulation,and may offer new directions for the treatment of cervical cancer through molecularly targeted therapy and gene therapy.Studies have shown that the cadherin family is involved in the development and progression of many tumours,but its role in cervical cancer and its mechanisms are still unclear.The aim of this study is to investigate the effect of the cadherin family on the proliferation,invasion and migration of cervical cancer cells and its molecular mechanisms,and to provide new targets and evidence for the treatment of cervical cancer patients.Methods:1.Based on TCGA database,differential analysis of expression levels of cadherin(CDH)family-related genes in cervical cancer tissues and para-cancer tissues was performed;2.By Kaplan-meier plotter database,CDH family gene expression levels and overall survival time were analyzed to evaluate the prognostic effect of cervical cancer patients;3.The expression of CDH3 m RNA was detected by quantitative polymerase chain reaction(q PCR)in fresh cervical cancer tissues;4.The effect of silencing CDH3 on the proliferation of Hela and C33 A cervical cancer cells was detected by CCK8 cell experimentt;5.The results of Transwell assay showed that knockdown of CDH3 expression inhibited the migration and invasion of cervical cancer cells;6.Based on TCGA database,the patients with cervical cancer were divided into low-expression group and high-expression group according to the median expression of CDH3,then the relevant genes were screened out via KEGG pathway;7.The effects of silencing and overexpression of CDH3 on PI3K/AKT pathway-related proteins in Hela and C33 A cervical cancer cells were analyzed by Western blot.Results:1.Five differentially expressed genes(CDH1,CDH3,CDH24,CDH18 and CDH15)were obtained by comparing the data of cases and controls downloaded by TCGA database;2.Survival analysis showed that the overall survival of cervical cancer patients with high expression of CDH3 and CDH18 was significantly worse than that of patients with low expression of CDH1,CDH24 and CDH15.There was no significant relationship between the expression level of CDH1,CDH24 and CDH15 and the overall survival of patients;3.q PCR showed that the expression level of CDH3 in cervical cancer tissues was significantly higher than that in adjacent tissues;4.The results of CCK8 assay showed that knocking down the expression of CDH3 would inhibit the proliferation of cervical cancer cells;5.The results of Transwell assay showed that knocking down the expression of CDH3 would inhibit the migration and invasion of cervical cancer cells;6.KEGG pathway analysis showed that CDH3 was closely related to PI3K/AKT pathway in cervical cancer;7.The results of Western blot showed that knockdown of CDH3 expression resulted in decreased phosphorylation levels of PI3K/AKT pathway-related proteins PI3 K and AKT,whereas overexpression of CDH3 resulted in increased phosphorylation levels of PI3 K and Akt.Conclusion:1.CDH3 is the most prominent CDH family gene overexpressed in cervical cancer,and its high expression is associated with poor prognosis of patients.2.Inhibition of CDH3 can decrease the proliferation,migration and invasion of cervical cancer cells..3.Reducing or increasing the expression level of CDH3 will lead to the corresponding inhibition or activation of PI3K/AKT pathway,which will affect the progression of cervical cancer,and CDH3 have the potential as an anti-tumor target of cervical cancer.