LncRNA expression profiles in HBV-transformed human hepatocellular carcinoma cells treated with a novel inhibitor of human La protein.

We previously identified a novel inhibitor of La protein, H11, which inhibited hepatitis B virus (HBV) replication by inhibiting the interaction between La protein and HBV RNA. However, the other cellular factors involved in this process remain unclear. To investigate the mechanism of H11-mediated inhibition of HBV infection, a lncRNA microarray analysis was performed using H11-treated and untreated stable HBV-expressing human hepatoblastoma HepG2.2.15 cells. The profiles of differentially expressed lncRNAs and mRNAs were generated and analysed using Gene Ontology (GO) and pathway analyses. The microarray data showed that 61 lncRNAs were upregulated, 74 lncRNAs were downregulated, 43 mRNAs were upregulated, and 44 mRNAs were downregulated in H11 treatment group when compared with the control group, and these results were consistent with qRT-PCR expression data. Bioinformatic analysis indicated that the differentially expressed lncRNAs were involved in RNA-mediated post-transcriptional gene silencing, regulation of viral genome replication and Jak-STAT signalling and apoptosis pathways. GO analysis showed that differentially expressed mRNAs were enriched in negative regulation of the Wnt signalling pathway and negative regulation of growth. Pathways analysis indicated that the differentially expressed mRNAs were involved in regulation of nuclear β-catenin signalling and target gene transcription, as direct p53 effectors, and in the peroxisome proliferator-activated receptors signalling and peroxisome pathways. Microarray data and qRT-PCR results indicated that H11 mediates inhibition of HBV replication by regulating the Wnt, β-catenin and PPAR signalling pathways.