No abstract

No abstract

Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5 CD8 T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5 CD8 T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5 CD8 T cells in peripheral blood, in which CXCR5 CD8 T cells were negatively correlated with the frequency of CXCR5 CD4 T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5 CD8 T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5 CD8 T cells. Unlike CXCR5 CD4 T cells, when incubated with naive CD19CD27 B cells, CXCR5 CD8 T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5 CD8 T cells in B cell-CXCR5 CD4 T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5 CD8 T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5 CD8 T cells tended to associate with low HBV DNA load, and the frequency of CXCR5 CD8 T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5 CD8 T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.

Aberrant microRNA (miRNA or miR) expression has been reported to contribute to the pathogenesis of hepatocellular carcinoma (HCC). However, the involvement of specific miRNAs in HCC remains to be elucidated. The present study aimed to investigate the potential role of miR-200b and the mechanism underlying its function in hepatocarcinogenesis. The results of the present study demonstrated that the expression levels of miR‑200b were significantly reduced in HCC tissue samples, as compared with normal liver (NL) and para‑tumorous (PT) tissue samples. The results also revealed that miR‑200b expression levels in HepG2 cells were significantly decreased compared with those in L02 cells. In addition, western blotting and reverse transcription‑quantitative polymerase chain reaction demonstrated that the expression levels of DNA methyltransferase 3a (DNMT3a), a possible target gene for miR‑200b, were significantly higher in HCC tissue samples, as compared with those in NL and PT tissue samples. Furthermore, the data suggested that DNMT3a was a direct target gene of miR‑200b. Upregulated miR‑200b expression in HepG2 cells led to a decrease in DNMT3a expression levels, and an inhibition of cell proliferation. These results suggested that miR‑200b has an important role in hepatocarcinogenesis and acts by downregulating DNMT3a expression. Thus, miR-200b may be a promising target for HCC treatment.

Background: Worldwide, hepatocellular carcinoma (HCC) accounts for 80-90% of all cases of primary liver cancer, and is one of the ten most common malignancies. This study used bioinformatics analysis to identify genes associated with patient outcome in stages I-IV HCC and the gene pathways that distinguished between normal liver and liver cells and HCC and human HCC cell lines. Material/Methods: Target genes were defined as those that had marketed drugs or drugs under development targeting a specific gene and acquired from the Clarivate Analytics Integrity Database. Differential expression gene analysis, co-expression network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, survival analysis and receiver operating characteristic (ROC) curve analysis were used to explore the similarities and differences in gene expression profiles, functional associations, and survival in stage I-IV HCC. Normal liver cells (HL-7702) and HCC cell lines (HepaRG, HepG2, SK-Hep1, and Huh7) were studied using Western blot and quantitative reverse transcription PCR (RT-qPCR). Results: Hierarchical gene clustering identified target genes that distinguished between HCC and normal liver tissue. For stages I-IV HCC, there were seven commonly upregulated target genes EPHB1, LTK, NTRK2, PTK7, TBK1, TIE1, and TLR3, which were mainly involved in immune and signaling transduction pathways. PTK7 was highly expressed in stage I-IV HCC and was an independent prognostic marker for reduced overall survival (OS). Conclusions: Bioinformatics analysis, combined with patient survival analysis, identified PTK7 gene expression as a potential therapeutic target and prognostic biomarker for all stages of HCC.