Preliminary screening and functional analysis of circular RNAs associated with hepatic stellate cell activation

Abstract Objective To screen for circular RNAs (circRNAs) that are associated with the activation of hepatic stellate cell (HSC) by monitoring changes in liver circRNA expression in a model of liver fibrosis. Methods The classic mouse model of CCl 4 -induced liver fibrosis was established and validated by histopathological examination. JS1 cells were activated by TGF-β1 to model HSC activation in vitro . Differentially expressed circRNAs in the fibrotic liver tissues and JS1 cells were determined using circRNA microarray, and some of those circRNAs were verified by RT-qPCR. The target genes of the above circRNAs were then predicted by bioinformatics analysis and summarized into a “circRNA-miRNA-mRNA” network diagram. Constructed plasmid mmu_circ_34116 siRNA was transfected to JS1 cells by Lipo2000, then we detected the expression changes of α-SMA. Results A total of 10,389 circRNAs were identified by microarray screening, and 69 differentially expressed circRNAs were detected in the fibrotic liver tissues with >2-fold difference in expression level relative to normal liver tissues ( P Conclusion The circRNAs expression profile of liver tissue had changed in fibrosis mouse model, and some of these circRNAs may be associated with HSC activation. For instance, mmu_circ_34116 would inhibit HSC activation.