lncRNA PVT1 promotes hepatitis B virus-positive liver cancer progression by disturbing histone methylation on the c-Myc promoter

摘要

Long noncoding RNA (LncRNA) PVT1 has recently been reported to be involved in the development of hepatocellular carcinoma (HCC). We aimed to elucidate the correlation of PVT1 with hepatitis B virus-positive HCC in the clinic, and the roles of PVT1 in liver cancer cell biology, as well as to investigate the underlying molecular mechanisms. qPCR analysis was performed to examine the expression of PVT1 in hepatitis B virus-positive HCC tissues and liver cancer cell lines. lncRNA PVT1 overexpression and knockdown were achieved by transfection of an overexpression vector or shRNA. Cell proliferation, colony formation, migration, apoptosis, and invasion capabilities were examined, accordingly. RNA pull-down assay was employed to examine the connection between PVT1 and the PRC2 complex. Chromatin immunoprecipitation was employed to test the combination with EZH2 protein and H3K27me3 level on the MYC promoter. The results revealed that upregulation of PVT1 was detected in hepatitis B virus-positive HCC tissues compared with that noted in the HBV-negative samples. lncRNA PVT1 enhanced cell proliferation, migration, and invasion in the hepatitis B virus-positive Hep3B cells rather than the hepatitis B virus-negative HepG2 cells. PVT1 was able to bind EZH2 and obstruct the recruitment of EZH2 to the promoter of MYC therefore promoting MYC expression by altering H3K37me3 status in Hep3B liver cancer cells, and EZH2 protein was negatively correlated with lncRNA-PVT1 expression. In conclusion, our results indicate that lncRNA PVT1 promotes hepatitis B virus-positive liver cancer progression by disturbing histone methylation on the MYC promoter, suggesting that lncRNA PVT1 may be a potential target for developing diagnostic and therapeutic strategies of hepatitis B virus-positive liver cancer at the early stages.