標題: MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis
作者: Tsai, Wei-Chih
Hsu, Sheng-Da
Hsu, Chu-Sui
Lai, Tsung-Ching
Chen, Shu-Jen
Shen, Roger
Huang, Yi
Chen, Hua-Chien
Lee, Chien-Hsin
Tsai, Ting-Fen
Hsu, Ming-Ta
Wu, Jaw-Ching
Huang, Hsien-Da
Shiao, Ming-Shi
Hsiao, Michael
Tsou, Ann-Ping
生物科技學系
生物資訊及系統生物研究所
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
公開日期: 1-八月-2012
摘要: "MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo restoration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 transcript. In addition, Mir122a(-/-) livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced disease manifestation and tumor incidence in Mir122a(-/-) mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC."
URI: http://hdl.handle.net/11536/16601
ISSN: 0021-9738
期刊: JOURNAL OF CLINICAL INVESTIGATION
Volume: 122
Issue: 8
結束頁: 2884
顯示於類別:期刊論文


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  1. 000307128600025.pdf