Microarray profiling of circular RNAs and the potential regulatory role of hsa_circ_0071410 in the activated human hepatic stellate cell induced by irradiation

Abstract

Radiation-induced liver fibrosis (RILF) is considered as a major complication of radiation therapy for liver cancer. Circular RNA (circRNA) has been recently identified as a functional noncoding RNA involving in various biological processes. However, the expression pattern and regulatory capacity of circRNA in the irradiated hepatic stellate cell (HSC), the main fibrogenic cell type, still remain unclear. A circRNA microarray was used to identify circRNA expression profiles in irradiated and normal HSC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the dysregulated circRNAs. Bioinformatic analyses including gene ontology (GO), KEGG pathway and circRNA/microRNA interaction network analysis were applied to predict the potential functions of circRNAs. Compared with the normal HSC, 179 circRNAs were found to be up-regulated and 630 circRNAs were down-regulated in irradiated HSC (fold change ≥2.0 and P<0.05). Six dysregulated circRNAs selected randomly were successfully verified by qRT-PCR. Bioinformatic analyses indicated that dysregulated circRNA might be involved in the cell response to irradiation and biological processes of hepatic fibrosis. Furthermore, inhibition of hsa_circ_0071410 increased the expression of miR-9-5p, resulting in the attenuation of irradiation induced HSC activation. In summary, this study revealed the expression profile and potential function of differentially expressed circRNAs in irradiated HSC, which provides novel clues for RILF study.