We used oxidative isotope-coded affinity tags (OxICAT) to investigate the global redox status of proteins in human papillomavirus (HPV)-related cervical cancer cells, in order to identify a potential target for gene therapy. Voltage-dependent anion channel 1 (VDAC1) was found to be highly oxidized in HPV-positive cervical cancer cells. VDAC1 expression correlated significantly with the invasion of cervical cancer, the grade of cervical intraepithelial neoplasia (CIN) and the expression of HPV16 E7 in CIN. Knockdown of VDAC1 in cell lines increased the rate of apoptosis, while overexpression of the VDAC1 (respectively) partly reversed the effect. Thus, VDAC1 may promote the malignant progression of HPV-related disease, and treatments designed to suppress VDAC1 could prevent the progression of HPV-induced cervical disease.

Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies.

Integration of the high risk human papillomavirus (HR-HPV) genome into host chromatin is an important step in cervical carcinogenesis. We identified HR-HPV integration sites within the human genome through detection of integrated papillomavirus sequences-PCR and assessed the role of high mobility group A 2 (HMGA2) in cervical carcinogenesis in clinical samples and cell lines. HPV integration sites were analyzed in 40 cervical cancer samples, while copy number variation and protein expression were assessed in 19 normal cervixes, 49 cervical intraepithelial neoplasia (CIN), and 52 cervical cancer samples. Overall, 25 HR-HPV integrating loci were detected in 24 cervical samples; HMGA2 was the only recurring integration site. Both HPV copy number and HMGA2 protein expression were higher in cervical cancer than CIN samples. Area under the curve (AUC) values for HMGA2 expression and HPV copy number were 0.910 (95% CI: 0.844-0.976) and 0.848 (95% CI: 0.772-0.923), respectively. Expression of Bcl-2 and Caspase 3 can indicate the cell proliferation and apoptosis. Transfection of HMGA2 siRNA decreased HMGA2 mRNA and protein expression, Bcl-2 expression, inhibited cell proliferation, and increased Caspase 3 expression and apoptosis in SiHa, CaSki and S12 cervical cancer cells. HMGA2 overexpression had the opposite effects. These results suggest that elevated HMGA2 expression is associated with transformation of CIN into cervical cancer and that HMGA2 might be a useful biomarker for assessing the risk of cervical lesion progression.

The current study was designed to quantitatively summarize the evidence for the strength of the associations between common IL-10 functional polymorphisms and skin cancer risk. Relevant publications concerning the associations between common IL-10 functional polymorphisms(-1082G>A, -819C>T and -592C>A) and skin cancer were retrieved by a comprehensive electronic literature search in PubMed, Web of Science, EBSCO, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database (CBM). The odds ratio (OR) and 95% confidence interval (CI) were utilized to assess the strength of the relationship. A total of 26 studies including 4090 cases and 4133 controls (-1082G>A, 10 studies with 1809 cases and 1830 controls; -819C>T, 7 studies with 862 cases and 957 controls; -592C>A, 9 studies with 1419 cases and 1346 controls) were enrolled in the meta-analysis. Overall, the results revealed a borderline decreased risk of skin cancer in heterozygote model (OR = 0.82, 95CI = 0.67-1.00, p = 0.05). The subgroup analysis also presented similar association for non-melanoma skin cancer in heterozygote model (OR = 0.67, 95CI = 0.50-0.91, p = 0.01). Moreover, the further analysis based on the histological type of non-melanoma skin cancer indicated a significantly decreased risk of BCC in allele model (OR = 0.67, 95% CI = 0.50-0.91, p = 0.02) and dominant model (OR = 0.68, 95% CI = 0.48-0.98, p = 0.04). However, neither overall analysis nor subgroup analysis based on cancer subtype revealed a significant association of -1082G>A or -592C>A polymorphisms with skin cancer. The present study suggested a potential association between IL-10 -819C>T polymorphism and decreased risk of skin cancer, but a lack of association for -1082G>A and -592C>A polymorphisms. Further invalidation is urgently needed.