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

Abstract

Summary 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.

Differential expression profile of long noncoding RNAs in chronic HBV infection: New insights into pathogenesis

“…However, many research studies indicated that lncRNAs might mediate the expression of neighboring and distantly located genes via cis/trans regulatory effects, respectively, and the genomic context could, therefore, provide important information about the potential functions of lncRNAs 7,20 . Therefore, most researchers always indirectly predict the functions of lncRNAs by performing GO and pathway analysis of their neighboring and distantly target genes 21,22 . However, to investigate the integrated functions of lncRNAs, we performed GSEA base on Pearson's correlation coefficient between the selected lncRNA and all mRNAs in this study.…”

“…7,20 Therefore, most researchers always indirectly predict the functions of lncRNAs by performing GO and pathway analysis of their neighboring and distantly target genes. 21,22 However, to investigate the integrated functions of lncRNAs, we performed GSEA base on Pearson's correlation coefficient between the selected lncRNA and all mRNAs in this study. Largely consistent with the results of enrichment analysis of the differentially expressed mRNAs, the top 10 upregulated and 10 downregulated lncRNAs were also primarily involved in the biotransformation process, such as fatty acid metabolism, amino acid metabolism, carbon metabolism, and drug metabolism.…”

“…7,20 Therefore, most researchers always indirectly predict the functions of lncRNAs by performing GO and pathway analysis of their neighboring and distantly target genes. 21,22 However, to investigate the integrated functions of lncRNAs, we per- inhibition of IL-10 has been proven to recover specific CD8 + T-cell response and accelerate virus eradication in in vivo and in vitro studies. 24,27 As shown in Figure 5B, IL-10 was positively and negatively correlated with five lncRNAs and two lncRNAs, respectively, indicating that these lncRNAs might participate in the molecular mechanism of CHB through mediating the functions of IL-10.…”

Study on the structure optimization and anti‐hepatitis B virus activity of novel human La protein inhibitor HBSC11

“…Recently, we used microarray and quantitative real‐time PCR to investigate the mechanism of H11‐mediated inhibition of HBV infection. The results showed that HBSC11‐induced inhibition of HBV replication was mediated via miR‐ 3912‐5p, miR‐6793‐5p, and miR‐7159‐5p and participation in the Wnt, beta‐catenin, and PPAR signaling pathways . Further research is underway on this subject.…”

Subversion of cellular autophagy during virus infection: Insights from hepatitis B and hepatitis C viruses

“…Many lncRNAs are reportedly dysregulated in HBV-related HCC and HBV/HBx expressing cells. 80,81 Most of the studies only focused on the dysregulation of lncRNA and a few of these have actually focused on the molecular mechanism. In HBV related HCC, two autophagy-related lncRNAs, HOTAIR and HULC were studied in detail.…”