CircRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of nonalcoholic steatohepatitis.

Zun Xiang,Chun-Yan Feng,Yi-Peng Chen,Xi Jin,You-Ming Li

doi:10.18632/oncotarget.12186

Zun Xiang, Chun-Yan Feng + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.12186

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Journal: Oncotarget	Publication Date: Sep 22, 2016
Citations: 165	License type: cc-by

Affiliation: Zhejiang University, Hangzhou Medical College

Abstract

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.

Highlights

Nonalcoholic steatohepatitis (NASH) is considered as an important stage of nonalcoholic fatty liver disease (NAFLD) that is characterized by lipid deposition in hepatocytes of liver parenchyma without alcohol overconsumption and composed of simple steatosis, NASH, fibrosis and cirrhosis with disease progression
Increasing evidences suggest that NASH acts as the “watershed” in NAFLD progress, where the percentage of progressing from NASH into liver fibrosis and end-stage liver diseases have greatly increased into 41% and 5.4%, respectively [1]
NASH mice model was successfully established after feeding Methionine and choline deficiency (MCD) diet for 4 weeks, as reflected by distinctive changes in serum biomarker and liver tissue

Summary

Introduction

Nonalcoholic steatohepatitis (NASH) is considered as an important stage of nonalcoholic fatty liver disease (NAFLD) that is characterized by lipid deposition in hepatocytes of liver parenchyma without alcohol overconsumption and composed of simple steatosis, NASH, fibrosis and cirrhosis with disease progression. Increasing evidences suggest that NASH acts as the “watershed” in NAFLD progress, where the percentage of progressing from NASH into liver fibrosis and end-stage liver diseases have greatly increased into 41% and 5.4%, respectively [1]. NASH is regarded as the major cause of cryptogenic cirrhosis. It is of clinical and theoretical importance for in-depth NASH study.

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