Regulation of HPV transcription

Human papillomavirus infection is associated with the development of malignant and benign neoplasms. Approximately 40 viral types can infect the anogenital mucosa and are categorized into high- and low-risk oncogenic human papillomavirus, depending on their association with the development of cervical carcinoma. High-risk human papillomavirus 16 and 18 are detected in 55% and 15% of all invasive cervical squamous cell carcinomas worldwide, respectively. Low-risk human papillomavirus 6 and 11 are responsible for 90% of genital warts and are also associated with the development of recurrent respiratory papillomatosis. Human papillomavirus preferentially infects mitotic active cells of the basal layer from both mucosal and cutaneous epithelium through microabrasions. The viral life cycle synchronizes with the epithelial differentiation program, which may be due, in part, to the binding of differentially expressed cellular transcription factors to the long control region throughout the various epithelial layers. This review aimed to summarize the current knowledge regarding the mechanisms by which viral gene expression is regulated and the influence of human papillomavirus heterogeneity upon this phenomenon. A better understanding of the regulatory mechanisms may elucidate the particularities of human papillomavirus-associated pathogenesis and may provide new tools for antiviral therapy.

Effect of HPV-16 LCR internal meCpG site demethylation on HPV positive head and neck tumor cells / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the effect of HPV-16 LCR internal meCpG site demethylation on HPV positive head and neck tumor cells. METHODS After 5-azoxy-2-deoxycytidine(5-Aza-2'-dc) demethylation treatment, the methylation status of CpG sites in the long regulatory region of UM-SCC47, CaSki and SiHa tumor cells was detected by BSP assay. The expression of HPV 16 E6 and E7 mRNA was detected by real-time PCR. The effects of 5-Aza-2'-dc on cell growth and apoptosis were detected. Using Lipolnfectamine RNAiMAX to transfect siRNA, the expression of E6 and E7 was silenced, and then the changes of biological state of cell proliferate inhibition, apoptosis and cycle were detected. RESULTS Cells treated with 5-Aza-2, -dc at a concentration of 0.5 μmol/L for 96 h had the best demethylation. After demethylation of 5-Aza-2'-dc, the expression levels of E6 and E7 mRNA in UM-SCC47 cells and CaSki cells were significantly decreased compared with the control group(t=1.356, 2.623, P=0.031, 0.005; t=1.798, 2.015, P=0.011, 0.009). The expression levels of E6 and E7 mRNA in SiHa cells were not significantly differences compared with the control group(t=1.591, 1.153, P=1.105, 0.753); After treated with 5-Aza-2'-dc, cells proliferation were significantly inhibited. After E6 and E7 expression was silenced, the growth of all three kinds of cells was inhibited. The apoptosis of all three kinds of cells were significantly increased, cells arrested in S phase and G2/M phase were significantly increased compared with the control groups, the difference were statistically significant. CONCLUSION After demethylation, the response of HPV-16 positive tumor cells with different methylation status in the long regulatory region is completely different, indicating that in the HPV-16 positive tumors, there may be some information about the methylation status in the long regulatory region Different tumor characteristics and mechanism of cancer.