RNA-seq Facilitates Quantitative Analysis of Wild Type and RXRα-silenced HepG2-NTCP Cell Transcriptomes

The goals of this study are to check mRNA levels of genes and pathways regulated by RXRα knocking down, and figure out their influences to HBV infection. The mRNA profiles of wild-type (WT) and RXRα knockdown (RXRα-KD) HepG2-NTCP cells were generated by deep sequencing using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the gene level with TopHat followed by Cufflinks. Using an optimized data analysis workflow, we mapped about 40 million sequence reads per sample to the human genome. We find arachidonic acid synthesis, retinol metabolism pathways and serveral other genes are regulated by RXRα knockdown. We also revealed that reduced gene expression in arachidonic acid (AA)/eicosanoids biosynthesis pathways, in particular one of the AA synthases Phospholipase A2 Group IIA (PLA2G2A), is associated with increased HBV infection. Moreover, we also found exogenous treatment of AA inhibits HBV infection. These data implicate the participation of AA/eicosanoids biosynthesis pathways in the regulation of HBV infection, and point to a novel potential strategy for host-targeted therapies against HBV. Examination of 2 different mRNA profiles in 2 cell lines. Reference to SRA study SRP121524 and BioProject PRJNA414179.