Functional Study of MicroRNA-7a Depletion Induced Zebrafish Early Onset of Non-alcoholic fatty liver disease

• Main Authors: Chang, Ching-He, 張靜合
• Other Authors: Her, Guor-Mour
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/88680702450712827170

碩士 === 國立臺灣海洋大學 === 生命科學暨生物科技學系 === 104 === MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play key roles in the regulation of gene expression. Recently, several researchers have reported that miRNA we links to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the progression to non-alcoholic steatohepatitis (NASH). NASH may progress to advanced-stages of hepatic fibrosis, cirrhosis and liver failure, and then causes of death and hepatocellular carcinoma (HCC). However, there is rarely known about specific therapies for NASH. To development of new target therapy is urgently needed. MicroRNA-7 (miR-7) plays an important role in the occurrence and development of tumors as a key tumor suppressor. Previous research indicated that mir-7a is down-regulated in ob/ob mouse liver and HNF4a-NF-jB feedback circuit including mir-7 is identified in HCC, miR-7 directly inhibits a number of oncogenic targets and impedes cancer progression in vitro and in vivo. Therefore, we designed a miR-7a sponge expression vector drove by liver specific promoter L-FABP combined fluorescent gene to establish transgenic fish. We show that miR-7-silencing activity is specifically knocked down in the transgenic fish liver. As the insights into our research aims for studying NAFLD, feeding these transgenic fish with high fat diet (HFD) and low fat diet (LFD) . We observed the accrual of fat in hepatocytes with Oil Red O staining. Our data shows that miR-7a sponge transgenic fishs have more lipid droplet accumulation in liver than WT with HFD and LFD. In the future, we will plan to analyze miR-7 target genes and of cell proliferation and cell apoptosis in transgenic fish, it can be expected to activities help the study of NAFLD.