No abstract

No abstract

T-helper (Th)17 cells, a new population of effector CD4(+) T cells, are characterized by the secretion of interleukin (IL)-17. It has been demonstrated that Th17 cells are distinct from Th1 and Th2 cells; they play important roles in the pathogenesis of numerous inflammatory and autoimmune diseases; and are closely related to host defense, tumorigenesis and transplant rejection. Moreover, it has been found that these cells have a close and intricate connection with the regulatory T cells, which play an important role in maintaining self-tolerance and down-tuning immune responses. In the present review, we find that they are significantly elevated in various kinds of liver diseases including liver autoimmunity and inflammatory diseases, alcoholic liver disease and hepatocellular carcinoma.

Background Worldwide, hepatocellular carcinoma (HCC) is a common solid tumor with a poor prognosis. HCC is often due to hepatitis B virus (HBV) infection. As yet, efficacious HCC treatment regimens for late-stage HCC patients are lacking. Therefore, the identification of more specific and sensitive biomarkers for its early diagnosis and treatment remains an urgent need. Methods Total RNAs from paired HBV-derived HCC tumors and adjacent peritumor tissues (APTs) were subjected to RNA sequencing (RNA-seq), and differentially expressed genes (DEGs) between HCC tumors and APTs were selected and verified. Results We identified 166 DEGs and found that eight top-ranked and verified DEGs (TK1, CTTN, CEP72, TRIP13, FTH1, FLAD1, CHRM2, AMBP) all contained putative OCT4 binding motifs in their promoter regions. TK1, TRIP13 and OCT4 were found to exhibit concurrent higher expression levels in HCC tumors than in APTs. The mRNA levels of TK1, TRIP13 and OCT4 in a cohort of 384 HCC samples from the TCGA database were all found to be negatively correlated with patient overall survival, relapse-free survival and progression-free survival, underscoring the HCC biomarker status of TK1 and TRIP13 on one hand, and implicating their association with OCT4 on the other hand. Furthermore, OCT4 proteins were found to bind to the promoters of both genes in vitro and in vivo. Knocking out OCT4 in HCC-derived cell lines reduced the expression of TK1 and TRIP13 and significantly decreased their tumorigenicity. Chao Ye, Xiaoqian Zhang and Xinyu Chen contributed equally to this work.