29 E6-P53 AND E7-RB co-mediated higher carcinogenic ability of HPV16 than HPV58 in cervical cancer. (18th September 2019) - Jian, Z
Abstract : Objectives: HPV16 presents most frequent infection and most powerful carcinogenic capacity in human cervix. HPV58 is more common in Asian women. The mechanism of HPV16 gaining higher carcinogenic ability than HPV58 is still unknown. Methods: We collected 4030 cervical exfoliated cell samples in our hospital. All the samples did HPV genotyping using HybriBio's proprietary flow-through hybridization technique and liquid-based cytology (LBC), and if necessary colposcopy-guided quadrant biopsies. Four plasmids containing E6 and E7 of HPV 16 and 58 were constructed and transfected into 293T and U2OS cells, respectively. Cell cycle, apoptosis, proliferation and invasion were detected by FCM, CCK8 detection and transwell assay, respectively. E6-P53 and E7-pRB co-expression and co-localization were detected by western blot and confocal immunofluorescence. Results: We found that the percentage of HPV16 in ≤LSIL group was 18.9% while HPV58 was 19.7%; HPV16 in HSIL group was 49.5% while HPV58 was 19.6%; HPV16 in cancer group was 65.3% while HPV58 was 9.0%. The proportion of early apoptosis in 293T cells with HPV58 E6/E7 overexpression (293THPV58over) was 7.9% and 6.85%, while 4.4% and 3.99% in 293THPV16over (all P<0.05), respectively. S phase was 42.68% and 45.36% in 293THPV58over, while 52.66 and 52.7% in 293THPV16over (all P<0.05). Moreover, decreased P53 and increased pRB expression in the nuclear was observed in 293THPV16over compared with 293THPV58over. Similar results were observed in U2OS cells. Conclusions: Our findings identified E6-P53 and E7-Rb co-mediated HPV16 gained higher carcinogenic ability than HPV58 in cervical cancer.