Transcription factor c-Rel regulated by E5 affects the whole process after HPV16 infection through miR-133a-modulated feedback loop aim at mir-379-369 cluster

Abstract

Background: During the development of cervical cancer, HPV infection causes a series of changes in transcription factors and microRNAs. But their relationships with pathogenic processes are not clear. Methods: Base on previous study, to analyse the relationship among HPV16 infection and the related transcription factors, related miRNAs, so as to further understand the molecular mechanism of HPV16 infection to cervical cancer, around the HPV16 related miRNAs we have reported, the methods of bioinformatics prediction, histology, cell model in vitro and molecular interaction were used for prediction and validation respectively Results: The results showed that NF-κB family members(c-Rel, p65 and p50) were identified as main HPV16rmiR-transcription factors. They have different expressive characteristics in cervical lesions and play tumorigenesis or progression roles in different periods of HPV16 infection. c-Rel, p65 and p50 act as mediators which link the HPV16 E5 and HPV16 related miRNAs. Among them, c-Rel affects the occurrence and progression of cervical cancer during whole HPV16 infection stage through miR133a-3p–modulated mir-379-369 cluster with a positive feedback way which targeted c-Rel itself and its positive regulator AKT3. Conclusion: So in the course of HPV16 infection, the E5, c-Rel, and miR-133a-3p form a positive feedback system which aim at mir-379-369 cluster for the whole process from HPV16 infection to cervical cancer.