ABSTRACT
Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.
Subject(s)
Antiviral Agents/administration & dosage , Autophagy-Related Protein 7/genetics , Carcinoma, Hepatocellular/virology , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Liver Neoplasms/virology , RNA, Long Noncoding/genetics , Aged , Antiviral Agents/pharmacology , Autophagy-Related Protein 7/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Disease Progression , Female , Genotype , Hepacivirus/drug effects , Hepacivirus/growth & development , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/metabolism , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome , Up-Regulation , Viral Load/drug effectsABSTRACT
Hepatitis C virus (HCV) infection is a major public health problem, having a high prevalence in Egypt. Leukemia and lymphoma have been associated with HCV infection. MicroRNA-155 (miR-155) has been reported to play a regulatory role in cancer, inflammation, and immune response to infection. The expression level of miR-155 in HCV viremic patients is controversial; although high miR-155 levels were demonstrated in HCV genotypes 1,2, and 3, low levels of miR-155 were detected in Egyptian patients with HCV genotype 4. Several studies have investigated the correlation between the levels of miRNA-155 and the replication of HCV, others have evaluated miRNA-155 as a prognostic biomarker in different types of cancer. No studies have investigated the impact of miRNA-155 knockdown on HCV pediatric patients associated with childhood acute lymphoblastic leukemia (ALL). We knocked-out the miR_155a in cultured polymorphonuclear cells (PBMCs) obtained from 60 children with ALL; 30 were associated with HCV-4 infection and 30 were HCV negative. The miR_155a, HCV viral load, and cell proliferation werre assessed in treated and untreated cells using TaqMan assay quantitative polymerase chain reaction. We found that miRNA-155 was significantly upregulated by seven folds in the HCV-4 associated ALL group; while being linked to high HCV viral load and leukemic burden, miR_155a knock-out can improve the disease outcome. We conclude that miR-155 is a critical miRNA that is considered a therapeutic target in pediatric HCV leukemic patients.
Subject(s)
Hepatitis C/metabolism , Hepatitis C/virology , MicroRNAs/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology , Cell Proliferation , Child , Egypt , Gene Expression Profiling , Genotype , Hepacivirus , Humans , Immunophenotyping , Neutrophils/metabolism , Prognosis , Viral LoadABSTRACT
OBJECTIVES: To evaluate in vitro antitumor effects of bee honey (BH) and Nigella sativa (NS) on HepG2 through their antioxidant and apoptotic activities. METHODS: HepG2 cell line was treated with different concentrations of diluted unfractionated BH and different concentrations of alcohol extract of NS. Exposure lasted for different time durations (6-72 hours), both dose-response and time course-response were conducted. Cell viability was tested by trypan blue exclusion test. Total antioxidant status and caspase-3 activity were estimated in the cell lysate. Nitric oxide levels were measured in culture supernatants of both treated and untreated HepG2 at all indicated times. RESULTS: Treatment of HepG2 cells with BH and NS leads to a significant decrease in both the number of viable HepG2 cells and the levels of nitric oxide on one hand, but improvement of the total antioxidant status and caspase-3 activity on the other, especially in HepG2 cells treated with higher doses of BH and NS (20% and 5000 µg/mL, respectively) and for longer duration (72 hours). CONCLUSIONS: BH and NS are effective in reducing the viability of HepG2 cells, improving their antioxidant status and inducing their apoptotic death.