Her Guor Mour, Hsu Chia-Chun, Hong Jiann-Ruey, Lai Chi-Yu, Hsu Meng-Chieh, Pang Hsi-Wen, Chan Sheng-Kai, Pai Wan-Yu
Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan.
Biochim Biophys Acta. 2011 Sep;1811(9):536-48. doi: 10.1016/j.bbalip.2011.06.011. Epub 2011 Jun 23.
Gankyrin is a small ankyrin-repeat protein that previous research has confirmed to be overexpressed in hepatocellular carcinoma (HCC). Although relevant literature has reported on gankyrin functions in cellular proliferation and tumorigenesis, the exact role of gankyrin is poorly understood in animal model systems. This study analyzed hepatic lipid accumulation in gankyrin transgenic (GK) zebrafish. Bromodeoxyuridine (BrdU)-positive cells were predominantly increased in the liver bud of GK larvae, indicating that gankyrin functionally promoted cell proliferation at the larval stage in GK fish. However, over 90% of the viable GK adults showed an increased lipid content, leading in turn to liver steatosis. Liver histology and oil red O staining also indicated the accumulation of fatty droplets in GK fish, consistent with the specific pathological features of severe steatosis. Molecular analysis revealed that gankyrin overexpression induced hepatic steatosis and modulated the expression profiles of four hepatic microRNAs, miR-16, miR-27b, miR-122, and miR-126, and 22 genes involved in lipid metabolism. Moreover, significantly increased hepatic cell apoptosis resulted in liver damage in GK adults, leading to liver failure and death after approximately 10months. This study is the first to report gankyrin as a potential link between microRNAs and liver steatosis in zebrafish.
甘基瑞因是一种小的锚蛋白重复序列蛋白，先前的研究已证实其在肝细胞癌（HCC）中过表达。尽管相关文献报道了甘基瑞因在细胞增殖和肿瘤发生中的功能，但在动物模型系统中，对甘基瑞因的确切作用仍了解甚少。本研究分析了甘基瑞因转基因（GK）斑马鱼的肝脏脂质积累情况。在GK幼虫的肝芽中，溴脱氧尿苷（BrdU）阳性细胞显著增多，表明甘基瑞因在功能上促进了GK鱼幼体阶段的细胞增殖。然而，超过90%存活的GK成鱼脂质含量增加，进而导致肝脏脂肪变性。肝脏组织学检查和油红O染色也表明GK鱼中存在脂肪滴积累，这与严重脂肪变性的特定病理特征一致。分子分析显示，甘基瑞因的过表达诱导了肝脏脂肪变性，并调节了四种肝脏微小RNA（miR-16、miR-27b、miR-122和miR-126）以及22个参与脂质代谢的基因的表达谱。此外，GK成鱼肝细胞凋亡显著增加导致肝脏损伤，约10个月后导致肝功能衰竭和死亡。本研究首次报道甘基瑞因是斑马鱼中微小RNA与肝脏脂肪变性之间的潜在联系。
