| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 99 === MicroRNA-122, a liver-specific abundant miRNA, is down-regulated in intrahepatic metastastic HCC. With both in vitro and in vivo experimentations, we demonstrated miR-122 as a tumor suppressor miRNA. To obtain insights into the physiological functions of mir-122, we generated a mutant mouse. The salient features of the mir-122-/- mice include multistep hepatocarcinogenesis from steatohepatitis, fibrosis to HCC, and extensive alteration of gene expression. We also performed pilot studies on embryonic fetal livers. Our preliminary results showed that although expressed at low level in the embryonic livers, deletion of mir-122 has clear impact on both the transcriptome of the early fetal livers and the metabolic zonation of livers.
The mechanisms regulating liver zonation are not fully understood but several determinants have been identified. Dicer1 is one of the regulators. Since mir-122 is a highly abundant hepatic miRNA we tested the expression patterns of several key zonation genes. In mir-122-/- livers, the distribution pattern of both pericentral and periportal genes is different that of the wild type liver. We examined the expression pattern of PV gene, glutamine synthetase and PP genes, E-cadherin and carbamoyl-phosphate synthase 1 as well as the expression profile of genes of Wnt signaling pathways. There is a general loss of zonal expression pattern and activation of Wnt5a, which signifies ??catenin independent signaling pathway.
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