Xiaobing Dou1,2, Luyan Feng1, Na Ying1, Qinchao Ding1, Qing Song1,2, Fusheng Jiang1,2, Cui Wang1,2, Songtao Li3,2. 1. College of Life Science, (XD, LF, NY, QD, QS, FJ, CW), Zhejiang Chinese Medical University, Hangzhou, China. 2. Molecular Medicine Institute, (XD, QS, FJ, CW, SL), Zhejiang Chinese Medical University, Hangzhou, China. 3. College of Basic Medicine & Public Health, (SL), Zhejiang Chinese Medical University, Hangzhou, China.
Abstract
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 nonalcoholic 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). Bioinformatics 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 up-regulated, and 4 were down-regulated 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 up-regulated 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 miR-19-5b was the only miRNA that was down-regulated 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_circ_1657/miR-19-5b may play a critical role in the development of ALD. Our study provides new insight into the future investigation and therapy on ALD.
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 nonalcoholic fatty liver disease. Whether circRNAs are involved explicitly in ALD remains unknown. METHODS: The expression profile of circRNAs in an ALDmouse model was depicted by circRNA sequencing. The dysregulated circRNAs were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics 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 up-regulated, and 4 were down-regulated 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 up-regulated 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 miR-19-5b was the only miRNA that was down-regulated in the ALDmice 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 ALDmice. mou_circ_1657/miR-19-5b may play a critical role in the development of ALD. Our study provides new insight into the future investigation and therapy on ALD.
Authors: Eric Vornholt; John Drake; Mohammed Mamdani; Gowon McMichael; Zachary N Taylor; Silviu-Alin Bacanu; Michael F Miles; Vladimir I Vladimirov Journal: Addict Biol Date: 2021-06-23 Impact factor: 4.093