Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell proliferation and migration. Pokemon knockdown inhibited the PI3K/Akt and c-Raf/MEK/ERK pathways and modulated the expression of various cell cycle regulators in HepG2 and Huh-7 cells. Therefore, Pokemon may also be involved in cell cycle progression in these cells. We confirmed that Pokemon silencing suppresses hepatocellular carcinoma growth in tumor xenograft mice. These results suggest that Pokemon promotes cell proliferation and migration in hepatocellular carcinoma and accelerates tumor development in an Akt- and ERK-signaling-dependent manner.

Objective. Nonalcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases. However, the pathogenesis of NAFLD is not still unclear. This study aims at evaluating the role of zinc finger and BTB domain‐containing 7A (ZBTB7A) in NAFLD. Methods. Western blotting, real‐time reverse transcription PCR (RT‐PCR), and immunohistochemistry were submitted to evaluate the level of ZBTB7A in the high fatty diet‐ (HFD‐) induced NAFLD mouse model. In vitro, the expression of ZBTB7A was assessed in oleic acid‐ (OA‐) induced HepG2 cells with western blotting and RT‐PCR. The luciferase reporter assay was used to estimate the effect of ZBTB7A on the SREBP1 and NF‐κB, and the ChIP assay was subjected to evaluate the direct binding to the SREBP1 promoter. Oil Red staining was used to detect lipid accumulation, and the ELISA was used to verify the levels of TG, T‐CHO, and MDA. ZBTB7A was knocked down with siRNA, and RT‐PCR was performed to analyze the lipogenesis‐, fatty acid transporter‐, and oxidation metabolism‐related genes expression. The levels of ZBTB7A in primary hepatocyte, Kupffer, and hepatic stellate cells (HSCs) were tested by RT‐PCR. Results. The upregulation of ZBTB7A expression was assessed in NAFLD mice, and ZBTB7A expression was positively correlated with TNFα, IL‐6, TG, T‐CHO, and MDA. ZBTB7A was highly expressed in the hepatocytes. In vitro, OA‐induced ZBTB7A expression and ZBTB7A expression were closely associated with SREBP1c. ZBTB7A could activate the promoter activity of SREBP1 and activate NF‐κB activity. Interestingly, the direct binding of ZBTB7A in the SREBP1 promoter was acquired in HepG2 cells. Inhibition of ZBTB7A expression could attenuate OA‐induced lipid accumulation, inhibit the expression of the lipogenesis‐related genes and fatty acid transporter genes, and promote the expression of oxidation metabolism‐related genes. Conclusion. ZBTB7A plays a significant role in the development process of NAFLD, and obesity‐induced upregulation of ZBTB7A promotes lipid accumulation through activation of SREBP1 and NF‐κB. ZBTB7A may be a potential novel target for the therapy of NAFLD.

The aim of this study was to investigate the effect of aplasia ras homolog member I (ARHI) on proliferation, apoptosis and the cell cycle in the pancreatic cancer cell line PANC-1. The study also aimed to examine the effect of ARHI on the activity of the nuclear factor (NF)-κB and to determine whether ARHI acts as a tumor suppressor in the development of pancreatic cancer by inhibiting the activity of NF-κB. A pIRES2‑EGFP‑ARHI vector, constructed by reverse transcrition (RT)‑PCR, was transiently transfected into the PANC-1 cells and analyzed for the expression of the ARHI protein by western blotting. A MTT assay was used to quantify cell proliferation, and apoptosis was analyzed by flow cytometry. The NF‑κB signaling pathway, specifically the pathway using the nuclear phosphorylated p65 isoform, was analyzed by western blotting. Expression of the ARHI protein was detected by western blotting subsequent to the PANC-1 cells being transiently transfected with the pIRES2‑EGFP‑ARHI construct. Cell proliferation was strongly inhibited in the PANC-1 cells transfected with pIRES2‑EGFP‑ARHI. The cell cycle assays indicated an increase in the number of cells at the G0/G1 phase and a decrease in the cells at the S phase, but the difference was not significant (P>0.05). Time course studies also indicated a marked increase in the apoptotic index following transient transfection, as well as a gradual decrease in the expression of the nuclear phosphorylated p65 protein. ARHI acts as a tumor suppressor by downregulating the NF‑κB signaling pathway, which results in the inhibition of cell proliferation, apoptosis and the cell cycle in the pancreatic tumor PANC-1 cell line.