HPV16 E6 gene mutation promotes the proliferation of cervical cancer cells by regulating the expression of BDNF/TrKB

Objective:Study on the mechanism of HPV16 E6 gene mutation promoting the proliferation of cervical cancer cells by influencing the expression of BDNF/TrkB.Methods:The expression levels of HPV16 E6 T350G,BDNF,TrkB and p53 mRNA in cervical cancer tissue samples and CINII cervical tissues were detected by Real-time PCR.HPV16 E6 T350G lentivirus(pLV5-HPV16 E6 T350G)and empty vector(pLV5-vector)were designed and constructed,and transfected with HCerEpiC cells,the expression levels of HPV16 E6 T350G,BDNF,TrKB and p53 mRNA were detected by Real-time PCR,and the expression levels of BDNF,TrKB,PI3K,pPI3K,AKT and pAKT protein were detected by western blot;cell proliferation was detected by MTT experiments.Results:Compared with cinii cervical tissue,HPV16 E6 T350G,BDNF and TrkB mRNA expression levels were all positive,while p53 mRNA expression was negative.After overexpression of HPV16 E6 T350G in HCerEpiC cells,it can up-regulate the expression levels of BDNF and TrKB protein and mRNA,and activate the PI3K/AKT signaling pathway which is the downstream of BDNF/TrKB,and reduce p53 protein expression levels;HPV16 E6 T350G overexpression can enhance the proliferation capacity of HCerEpiC cells.Conclusion:Overexpression of HPV16 E6 T350G can promote the proliferation of cervical cancer cells,which may be related to the upregulation of BDNF/TrKB expression,the activation of PI3K/AKT signaling pathway,and the decrease of p53 expression.