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"Liver-on-a-Chip" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection
Published on: February 19, 2019
Comprehensive Analysis of the mRNA-lncRNA Co-expression Profile and ceRNA Networks Patterns in Chronic Hepatitis B
Wenbiao Chen1, Chenhong Lin1, Lan Gong1
11State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China; 2St. George and Sutherland Clinical School, University of New South Wales, SydneyNSW2052, Australia.
Background:
Long non-coding RNAs (lncRNAs) are emerging as important regulators in the modulation of virus infection by targeting mRNA transcription. However, their roles in chronic hepatitis B (CHB) remain to be elucidated.
Objective:
The study aimed to explore the lncRNAs and mRNA expression profiles in CHB and asymp-tomatic HBsAg carriers (ASC) and construct mRNA-lncRNA co-expression profile and ceRNA net-works to identify the potential targets of diagnosis and treatment in CHB.
Methods:
We determined the expression profiles of lncRNAs and mRNAs in CHB and ASC using mi-croarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) path-way enrichment analyses were performed to explore their function. We also constructed co-expression, cis-regulatory, and competing endogenous RNA (ceRNA) networks with bioinformatics methods.
Results:
We identified 1634 mRNAs and 5550 lncRNAs that were differentially expressed between CHB and ASC. Significantly enriched GO terms and pathways were identified, many of which were linked to immune processes and inflammatory responses. Co-expression analysis showed 1196 relation-ships between the top 20 up/downregulated lncRNAs and mRNA, especially 213 lncRNAs interacted with ZFP57. The ZFP57-specific ceRNA network covered 3 lncRNAs, 5 miRNAs, and 17 edges. Cis-correlation analysis showed that lncRNA T039096 was paired with the most differentially expressed gene, ZFP57. Moreover, by expending the clinical samples size, the qRT-PCR results showed that the expression of ZFP57 and T039096 increased in CHB compared to ASC.
Conclusion:
Our study provides insights into the roles of mRNA and lncRNA networks in CHB, high-lighting potential applications of lncRNA-T039096 and mRNA-ZFP57 for diagnosis and treatment.
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