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Integral miRNA-mRNA analysis indicates novel therapeutic strategy for autoimmune liver diseases
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R. Nakagawa1,2,
N. Kato1,
M. Zeniya2,3 |
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1Division of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, 2Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, 3Sanno Medical Center, Sanno Hospital, International University of Health and Welfare |
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| Autoimmune liver diseases(ALDs), representatively primary biliary cholangitis(PBC) and autoimmune hepatitis(AIH), are complicated diseases based on unknown mechanisms of autoimmunity. To elucidate the mechanism of autoimmunity in ALDs, various studies based on genomics, transcriptomics, and epigenetics have been performed. Recent our integral transcriptomic-epigenetic analysis is implying the novel pathogenesis and therapeutic targets of ALDs. Dysregulation of microRNA(miRNA), as an epigenetic regulator, has been reported in several tissues of ALDs. However, specifying the miRNA function is a thorny subject in miRNA analysis. Therefore, we have performed an integral miRNA-mRNA analysis to reveal the pathological functions of miRNAs in ALDs. In PBC, we profiled miRNA-mRNA expression in CD4 T-cells using integral analysis. Then, it was revealed that miR-425 acted as an inflammatory regulator of PBC via N-Ras upregulation. Therefore, the restoration of decreased miR-425 or the suppression of N-Ras could be an immunotherapeutic strategy against PBC. Secondly, we profiled miRNA-mRNA expression in CD4 T-cells of AIH. Interestingly, miRNA-mRNA profiles in AIH were completely different from those in PBC. Moreover, a miRNA was correlated with JAK-STAT signaling in CD4 T-cells of AIH. In conclusion, integral transcriptomic-epigenetic analysis could disclose novel mechanisms of ALDs and suggest potent therapeutic targets in ALDs. |
Index Term 1: Autoimmune liver diseases
Index Term 2: microRNA |
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