In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4705-4705
Abstract:
MicroRNAs (miRNAs), inhibitors of gene expression, participate in diverse biological functions and in carcinogenesis. MicroRNA-122, a liver-specific miRNA, is known to regulate lipid metabolism and tumorgenesis and is down-regulated in the intrahepatic metastastic HCC. To obtain insights into the physiological function of miR-122, we successfully generated the mir-122-/- mutant mouse (122KO). 122KO mice are viable with reduced serum cholesterol, elevated alkaline phosphatase and portal infiltration. Collagen deposition suggested minor fibrosis in 122KO livers. 122KO mice have distinctly different lipid metabolism. The levels of cholesterol and triglyceride are low in serum but high in liver tissue. Lipoprotein analysis revealed that 122KO mice have defect in VLDL transport. These results indicate that mir-122 deletion generated pathological features reminiscent that of nonalcoholic fatty liver disease (NAFLD) in human. In addition, mir-122 deletion is also prone to hepatocarcinogenesis. Liver tumors developed at age of 11 months in 5/5 mice. Expression of many genes was affected by mir-122 deletion. Pronounced changes are found in genes contributing to inflammation, cholestasis, fetal antigens, loss-of-imprinting and most importantly, expression of genes for metabolism of lipid and carbonhydrate are downregulated. The drastic change of transcriptome likely contributes to the pathological features presented in mir-122 knockout mice. We believe that 122KO mouse is a potential model for human HCC. This mouse model will provide a great opportunity to evaluate the physiological functions of mir-122 in hepatocyte differentiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4705. doi:10.1158/1538-7445.AM2011-4705
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-4705
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
