학술논문
Serum miR-379 expression is related to the development and progression of hypercholesterolemia in non-alcoholic fatty liver disease.
Document Type
Article
Author
Okamoto, Kinya; Koda, Masahiko; Okamoto, Toshiaki; Onoyama, Takumi; Miyoshi, Kenichi; Kishina, Manabu; Matono, Tomomitsu; Kato, Jun; Tokunaga, Shiho; Sugihara, Takaaki; Hiramatsu, Akira; Hyogo, Hideyuki; Tobita, Hiroshi; Sato, Shuichi; Kawanaka, Miwa; Hara, Yuichi; Hino, Keisuke; Chayama, Kazuaki; Murawaki, Yoshikazu; Isomoto, Hajime
Source
Subject
*FATTY liver
*RECEIVER operating characteristic curves
*SOMATOMEDIN C
*CIRRHOSIS of the liver
*BLOOD cholesterol
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Language
ISSN
1932-6203
Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker. Methods: Eighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control. One patient was excluded due to low RT-PCR signal. Results: Compared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, low-density-lipoprotein cholesterol and non-high-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism–related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379. Conclusions: Serum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD. [ABSTRACT FROM AUTHOR]