CircRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of nonalcoholic steatohepatitis
Oncotarget
Jin,X Feng,CY Xiang,Z Chen,YP Li,YM
The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as "miRNA sponge". Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out. The overlapped predicted miRNAs as downstream targets of circRNAs and upstream regulators of mRNAs were verified by qRT-PCR and final circRNA-miRNA-mRNA network was constructed. Gene Ontology (GO) and KEGG pathway analysis were further applied to enrich the huge mRNA microarray data. To sum up, there were 69 up and 63 down regulated circRNAs as well as 2760 up and 2465 down regulated mRNAs in NASH group, comparing with control group. Randomly selected 13 of 14 mRNAs and 2 of 8 circRNAs were successfully verified by qRT-PCR. Through predicted overlapped miRNA verification, four circRNA-miRNA-mRNA pathways were constructed, including circRNA_002581-miR-122-Slc1a5, circRNA_002581-miR-122-Plp2, circRNA_002581-miR-122-Cpeb1 and circRNA_007585-miR-326-UCP2. GO and KEGG pathway analysis also enriched specific mRNAs. Therefore, circRNA profile may serve as candidate for NASH diagnosis and circRNA-miRNA -mRNA pathway may provide novel mechanism for NASH.
非酒精性脂肪肝炎的circRNA表达模式及circRNA-miRNA-mRNA网络在发病机制中的作用
仍然不清楚非酒精性脂肪肝炎（nonalcoholic steatohepatitis，NASH）的发病机制，由于circRNA作为“miRNA海绵”的积极作用，考虑circRNA参与非酒精性脂肪肝炎。因此，我们旨在研究NASH的circRNA表达谱，并进一步构建circRNA-miRNA-mRNA网络以进行深入机制探索。简单地说，通过甲硫氨酸和胆碱缺乏（Methionine and choline deficiency，MCD）饮食喂养建立NASH小鼠模型。通过微阵列初筛肝脏circRNA和mRNA表达谱，紧接着执行qRT-PCR验证。重叠的预测miRNAs作为circRNAs的下游靶，和mRNAs的上游调节因子，通过qRT-PCR验证，最后构建circRNA-miRNA-mRNA网络。进一步执行基因本体论（Gene Ontology，GO）和KEGG通路分析以富集巨大的mRNA微阵列数据。总之，与对照组相比，在NASH组中有69个上调和63个下调circRNAs，以及2760个上调和2465个下调mRNAs。随机挑选了14个mRNAs和8个circRNAs，其中qRT-PCR成功验证了3个mRNAs和2个circRNAs。通过重叠的预测miRNA确证，构建了4个circRNA-miRNA-mRNA通路，包括circRNA_002581-miR-122-Slc1a5、circRNA_002581-miR-122-Plp2、circRNA_002581-miR-122-Cpeb1和circRNA_007585-miR-326-UCP2。GO和KEGG通路分析也富集特定mRNAs。因此，circRNA表达谱可能充当NASH诊断的候选者，并且circRNA-miRNA-mRNA通路可能为NASH提供了新机制。
http://dx.doi.org/10.18632/oncotarget.12186
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341813/pdf/oncotarget-07-66455.pdf
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