Long noncoding RNA PVT1 inhibits interferon-alpha mediated therapy for hepatocellular carcinoma cells by interacting with signal transducer and activator of transcription 1

Long noncoding RNA (LncRNA) PVT1 has recently been reported to be involved in the development of hepatocellular carcinoma (HCC) and hsigh expression of oncogenic PVT1 is associated with poor prognosis of HCC. Interferon-alpha (IFN-alpha) has been used in clinic for HCC therapy. However, whether PVT1 is involved in the IFN-alpha therapy for HCC is completely unknown. Our study found that high PVT1 expression in HCC cells is associated with high unmethylation in PVT1 promoter region. IFN-alpha treatment further increases PVT1 expression in HCC cells by enhancing H3K4me3 modification on the promoter. Furthermore, PVT1 knockdown enhances IFN-alpha-induced HCC cell apoptosis by promoting phosphorylation of signal transducer and activator of transcription 1 (STAT1) and upregulating IFN-stimulated genes expression. Moreover, PVT1 specifically interacts with STAT1 in HCC cells. Taken together, these results for the first time indicate that IFN-alpha treatment promotes oncogenic PVT1 expression in HCC cells, which interacts with STAT1 to inhibit IFN-alpha signaling, ultimately blocking IFN-alpha-induced cells apoptosis, suggesting that IncRNA PVT1 may be a potential target to improve IFN-alpha-mediated HCC immunotherapies. (C) 2018 Published by Elsevier Inc.