RNA sequencing revealed a comprehensive circular RNA expression profile in a mouse model of alcoholic liver disease.
BACKGROUND AND AIMS
Alcoholic liver disease (ALD) is the most common liver disease and a severe mortality burden in the world. However, ALD is rarely detected at its early stages. Thus, exploration of an early event for ALD may help the prognosis and further therapy of ALD. Several circRNAs were proven as novel molecular biomarkers for the progression of chronic non-alcoholic fatty liver disease. Whether circRNAs are involved explicitly in ALD remains unknown.


METHODS
The expression profile of circRNAs in an ALD mouse model was depicted by circRNA sequencing. The dysregulated circRNAs were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatic and circRNA/microRNA (miRNA) crosstalk analyses were applied to predict the potential functions of circRNAs. Finally, the miRNA expression was confirmed by miRNA sequencing.


RESULTS
Compared with the control group, 6 members of circRNAs were upregulated, and 4 were downregulated in the ALD model. GO enrichment analyses revealed these circRNAs were predominantly enriched in the endoplasmic reticulum, arachidonic acid metabolism, and cytochrome P450 metabolism pathway. Among these circRNAs, the differential expression of 5 circRNAs was validated and consistent with qRT-PCR, and only the upregulated mou_circ_1657 is included in the circBase. Further, the crosstalk analysis of circRNA-miRNA revealed 7 miRNAs were targeted by mou_circ_1657, of which miR19-5b was the only miRNA that was downregulated in the ALD mice according to the miRNA sequencing data, suggesting it needs further attention in ALD.


CONCLUSIONS
This study demonstrates that a cluster of circRNAs is aberrantly expressed in the livers of ALD mice. mou-circRNA-1657/miR19-5b may play a critical role in the development of ALD. Our study provides new insight into the future investigation and therapy on ALD.