lncRNA-CD160 decreases the immunity of CD8+ T cells through epigenetic mechanisms in hepatitis B virus infection.

The transfer and development of chronic hepatitis B virus (HBV) infection is associated with the T cell immune response, therefore investigating the key regulators of cell immune response is needed to improve chronic HBV treatment. Blood samples from patients with chronic HBV infection were used to confirm the correlation between HBV infection stage and CD160 receptor expression levels in CD8+ T cells, the CD8+ T cells are used to research the mechanism of T cell immune response modulation, moreover, C3H/HeN mice with reduced CD160 expression levels were used to investigate the association between long non-coding (lnc)RNA-CD160 and HBV infection. Long non-coding (lnc)RNA-CD160 and histone-modification enzyme gene histone deacetylase 11 (HDAC11) expression levels were negatively associated with CD160 expression. lncRNA-CD160 can inhibit the secretion of IFN-γ and TNF-α through HDAC11 recruitment and bind to HDAC11 to form a complex on the promoters of IFN-γ and TNF-α. The HDAC11, IFN-γ and TNF-α form a complex and enhance the methylation of H3K9Me1, chromatin changes into the heterochromatin and the transcription of IFN-γ and TNF-α is blocked; moreover, the HDAC11/IFN-γ/TNF-α complex can also inhibit the secretion of IFN-γ and TNF-α in CD160- CD8+ T cells and suppresses the function of CD8+ T cells. Furthermore, small interfering RNA targeting lncRNA-CD160 can block HBV infection progression. lncRNA-CD160 acts as an immune suppressive factor and is expressed at a high level in peripheral blood CD8+ T cells of HBV infected patients. Furthermore, high expression levels of lncRNA-CD160 can contribute to the inhibition of IFN-γ and TNF-α secretion in CD8+ T cells and decrease the immune response of CD8+ T cells. Therefore, lncRNA-CD160 may become a new target for immunotherapy of chronic HBV infection in the future and may provide a new therapeutic strategy for the treatment of HBV infection.

Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1.

Although it is known that Phenazine biosynthesis-like domain-containing protein (PBLD) expression is downregulated in hepatocellular carcinoma (HCC), its biological function is unclear. Additionally, no agents capable of upregulating PBLD exist. In the current study, the relationship between PBLD and HCC was analyzed using clinicopathological specimens. A HCC cell model, microarray analysis and an animal model were used to verify the therapeutic effect of cedrelone on HCC. The present study demonstrated that PBLD inhibited HCC progression. Furthermore, the present study revealed that cedrelone possessed treated-HCC capabilities via targeted PBLD overexpression. The epithelial-mesenchymal transition phenotype and growth rate were inhibited and the apoptosis ratio was promoted by cedrelone following PBLD overexpression. The Ras and Ras-proximate-1 signaling pathways were also determined to be regulated by cedrelone via PBLD activation in HCC. PBLD may therefore be an independent predictor of HCC progression and a novel target for HCC treatment. Additionally, the PBLD activator, cedrelone, may be a potential drug for HCC treatment in the future.

Adjuvant pegylated interferon therapy improves the survival outcomes in patients with hepatitis-related hepatocellular carcinoma after curative treatment: A meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers and the second leading cause of cancer-related deaths in men worldwide. Surgical resection of HCC remains the mainstay treatment procedure. As a result of hepatitis viral infection, the postoperative survival outcome in patients with HCC is not satisfactory. Recently, studies have reported that due to its treatment effect on hepatitis infection, pegylated interferon (Peg-IFN)-based therapy could improve the survival outcome after the treatment of hepatitis-related HCC. However, the postoperative effect of this regimen on the survival outcomes in patients with hepatitis-related HCC remains debatable. The present study conducted a meta-analysis to evaluate the effects of adjuvant Peg-IFN-based therapy on the survival outcomes in patients with hepatitis-related HCC after the curative treatment. METHODS: A systematic search was conducted to identify studies on the survival outcomes in patients with hepatitis-related HCC after a curative treatment with adjuvant Peg-IFN. PubMed, EmBase, and Cochrane Library databases were searched until September 20, 2017. The retrieved studies were independently assessed by 2 reviewers, to identify the potentially eligible studies and extract data of interest. STATA software (Version 10.0, STATA Corporation, College Station, Texas) software was used for all statistical analyses. RESULTS: The pooled results showed that adjuvant Peg-IFN-based therapy improved the 3- and 5-year recurrence-free survival (RFS) rates of patients with hepatitis-related HCC (3-year RFS, HR = 0.80; 95% CI: 0.64-0.99, P = .04; P = .81 for heterogeneity; 5-year RFS, HR = 0.82; 95% CI: 0.67-0.99, P = .04; P = .84 for heterogeneity). For the 5-year overall survival (OS) outcomes of Peg-IFN therapy for hepatitis-related HCC after the curative treatment, the pooled results showed a significant difference between the 2 groups (HR = 0.67; 95% CI: 0.47-0.97, P = .03; P = .99 for heterogeneity). CONCLUSIONS: Adjuvant Peg-IFN-based therapy could improve the RFS and OS outcomes in patients after curative treatment of hepatitis-related HCC, with no severe adverse effects.