Application Of Hi-C Technology In Determining The Effects Of Human Papillomavirus 16 Integration On 3D Genome Architecture Of Cervical Cancer Cell Line SiHa

Objectives: We investigated the changes of three dimensional genome architecture of cervical cancer cell line SiHa after human papillomavirus 16(HPV16)integration and threw light on the relationship between high risk HPV integration and cervical carcinogenesis.Methods: Normal cervical epithelial cells collected from hysterectomy for benign lesions such as uterine myoma and adenomyoma were cultured in vitro as a control.Hi-C technology,RNA-seq and CHIP-seq were used for joint sequencing analysis of control and SiHa.Results:(1)Compared with control,the 3D genome architecture of SiHa was nearly the same,for example,the size and number of TAD,and the compartments were also conserved,80% of which were unchanged between control and SiHa.(2)Contrasted with control,the TAD and compartments near the HPV16 integration site were altered and the interactions of integration site among intrachromosomal and interchromosomal region were different in SiHa.(3)The compartments near PDE3 A gene were switched on from the compartment B in control to compartment A in SiHa and were associated with upregulated gene expression and the signals of active markers were increased and those of inactive markers were decreased in SiHa,and prognosis analysis suggested that those patients with high expression of PDE3 A had shorter overall survival time.Conclusions: HPV16 integration in SiHa had effects on the 3D genome architecture,mainly the changes of compartment,TAD and interactions,and eventually cervical cancer associated gene PDE3 A further affected the prognosis of cervical cancer patients.