HBV HBx-Downregulated lncRNA Attenuates Cell Proliferation by Interacting with Vimentin.

Hepatitis B virus (HBV) infection is closely related to hepatocellular carcinoma (HCC) development. To investigate the mechanism of HBV causing HCC, we previously analyzed the transcription of the HBV-transgenic cell line HepG2-4D14 and parental HepG2 cells and identified a subset of long noncoding RNAs (lncRNAs) differentially expressed between them. In this study, we focus on lncRNA , as it is significantly downregulated in HepG2-4D14 cells and in liver tissues of HCC patients, and positively correlated with survival. We found that HBV-encoded HBx can reduce the transcription of . Functional analysis showed that the overexpression of inhibits proliferation, migration and invasion of HepG2 cells while the knockdown of promotes these processes. By taking the approach of RNA immunoprecipitation (RIP) and mass spectrometry, we identified that can interact with vimentin. Further studies demonstrated that negatively affects the vimentin network extension and causes more rapid subunit exchange and lower stability of vimentin filaments. In addition, can reduce the amount of insoluble vimentin within cells, which suggests that interfers with vimentin polymerization. These data indicate that can inhibit the assembly of vimentin filament. Thus, we revealed that HBV HBx-downregulated , which suppresses cell proliferation and migration by negatively regulating the formation of vimentin filament. Taken together, is a potential tumor suppressor that may restrain HBV-related HCC development.