Dyskerin (encoded by the DKC1 gene) is an essential nucleolar protein involved in cell proliferation, where it is required for the pseudo-uridylation of ribosomal RNA (rRNA) molecules and the stabilization of the telomerase RNA component. Dyskerin expression has been reported to predict poor survival in some cancer patients. The aim of the present study was to analyze the expression of dyskerin in hepatocellular carcinoma (HCC) and to determine its correlation with clinicopathologic features, including the survival of patients with HCC. Dyskerin protein expression was detected by immunohistochemistry in paraffin sections of 252 HCC cases and 80 noncancerous liver tissues. The correlation was analyzed between dyskerin expression levels and clinicopathologic variables and prognosis. Dyskerin protein was significantly overexpressed in HCC tissues when compared to noncancerous liver tissue. Dyskerin overexpression was positively correlated with the hepatitis B surface antigen status, serum alpha-fetoprotein, and advanced clinical stage in HCC patients. A survival analysis indicated that HCC patients with higher dyskerin expression had a significantly shorter overall survival and 5-year survival time when compared to those with low expression. A multivariate analysis suggested that dyskerin overexpression was an independent factor for prognosis (hazard risk, 2.912; P = 0.007). Expression of DKC1 mRNA was measured by quantitative RT-PCR in 80 HCC and 50 non-cancerous tissues. The relationship between DKC1, TERT, MKI67, and MYC mRNA expression in HCC tissues was also evaluated. DKC1 mRNA was significantly overexpressed in HCC tissues and showed a significant correlation with MKI67 and MYC mRNA but a weak correlation with TERT mRNA. Dyskerin overexpression in HCC patients was correlated with MYC and MKI67 expression and showed a possible involvement in the tumorigenic process. Dyskerin overexpression may be an unfavorable prognostic factor in patients with HCC.

The aim of the present work was to perform a meta-analysis to evaluate the association between the interleukin 10 (IL-10) −819C/T (rs1800871) polymorphism and cancer risk. A total of 73 studies, including 15,942 cancer cases and 22,336 controls, were identified in this meta-analysis. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Overall, no significant association was identified between the IL-10 −819C/T polymorphism and cancer risk. In the subgroup analyses, the T allele and TT genotype were associated with a moderately reduced cancer risk in the Asian population (T allele vs. C allele: OR=0.93, 95%CI: 0.87, 0.99; TT vs. CC: OR=0.86, 95%CI: 0.76, 0.98; TT vs. CT/CC: OR=0.90, 95%CI: 0.82, 0.98). Individuals who were homozygous for the T allele (TT) were found to be associated with significantly reduced gastric cancer risk in the Asian population. The heterozygous variant (CT) and the dominant model (TT/CT vs. CC) were associated with an increased risk for cervical and ovarian cancer. However, the IL-10 −819C/T polymorphism was not significantly associated with breast cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, prostate cancer, lymphoma, or melanoma. The depressed cancer risk of the TT genotype occurred in the studies of hospital-based case-control studies and the studies recruited less than 500 subjects, but no statistically significant results were found in the stratified analyses using genotyping method. The results suggest that the IL-10 −819TT genotype may be a protective factor for cancer in Asians, especially gastric cancer. In contrast, the CT genotype and the dominant model could be risk factors for cervical and ovarian cancer. The importance of stratifying by ethnicity, cancer type, study design, and sample size needs to be standardized in future studies, together with considering the association between the IL-10 −819C/T polymorphism and cancer risk. Furthermore, the linkage of −819C/T with other polymorphisms of the IL-10 gene may help explain the variability in findings.

AIM: To investigate the phototoxic effect of long-term excessive narrow-band blue light in staurosporine-induced differentiated retinal ganglion cells-5 (SSRGC-5). METHODS: SSRGC-5 cells were divided into two groups, blue light group (BL group) and control group. Cell viability was assessed by using CCK-8 assay. Metabolic profile analysis was performed by using Seahorse extracellular flux analyzer. Mitochondria ultrastructure were studied via transmission electron microscope (TEM). Mitochondria contents and oxidative stress was evaluated by flow cytometry. Western blotting was performed to monitor the changes in mitogen-activated protein kinases (MAPK) pathway and PI3K/AKT pathway. RESULTS: Blue light caused morphological changes of SSRGC-5 cells. The cell viability was significantly decreased from 3h in BL group. Intercellular ROS and mitochondrial superoxide levels were increased following blue light exposure. Metabolic profiling identified blue light induced SSRGC-5 cells to have severely compromised mitochondrial function. This was accompanied by impaired mitochondrial ultrastructure and remodeling, increased expression of the mitochondrial related proteins, and increased glycolysis as compensation. Moreover, the results showed that blue light induced higher expression of p-p38, p38, p-JNK, p-ERK, p-c-Jun, c-Jun, and p-AKT. CONCLUSION: These findings indicate that excessive narrow-band blue light induces oxidative stress and mitochondrial metabolic remodeling dysregulate in SSRGC-5 cells. Activated MAPK and AKT signaling pathways are involved in this process.

Purpose: Blue light has been previously demonstrated to induce injury of retinal cells. The cellular responses to nonlethal blue light exposure for each type of retinal cell are of particular interest but remain undetermined. Based on the doses of blue light reported in previous research to be nonlethal to retinal pigment epithelial cells, here we investigated whether and to what extent such doses of blue light are cytotoxic to staurosporine-differentiated RGC-5 cells. Methods: RGC-5 cells were differentiated for 24 hours using 200 nM staurosporine. The resulting cells were cultured and exposed to blue light at three different energy levels (1, 10, and 50 J cm⁻²). Cellular morphologies were investigated with an inverted microscope and cell viability was assessed with a Cell Counting Kit-8 (CCK-8) assay. The generation of intracellular reactive oxygen species (ROS) was evaluated by H2DCFDA. After loading of MitoTracker Green FM dye, the mitochondrial contents were analyzed using flow cytometry. The lactate dehydrogenase (LDH) activities in the media were also measured. The level of lipid peroxidation was determined by measuring the amount of malondialdehyde (MDA). Results: Treatment of the cells for 24 hours with 200 nM staurosporine successfully induced the differentiation of RGC-5 cells. No morphological changes were observed in the ssdRGC-5 cells exposed to blue light at 50 J cm⁻², which was the highest energy level tested. Exposure of the ssdRGC-5 cells to this energy level of blue light did, however, decrease their numbers by approximately 72.1% compared to the numbers of such cells found after being left in the dark. Remarkably, the levels of ROS generation and mitochondrial contents were, respectively, increased to 142% and 118% of those of the control by a 10 J cm⁻² exposure of blue light. The LDH activities and MDA levels exhibited no obvious changes in the blue light-exposed ssdRGC-5 cells compared to the control cells. Conclusions: In vitro nonlethal blue light exposure led to cellular damage of staurosporine-differentiated RGC-5 cells. These increases in oxidative stress and mitochondrial content were the early steps of the cellular response to the exposure of relatively low doses (10 J cm⁻²) of blue light.