生物
小RNA
癌症研究
癌变
癌症
肝癌
细胞周期
细胞凋亡
癌细胞
肝细胞癌
免疫学
基因
遗传学
作者
Janaiah Kota,Raghu R. Chivukula,Kathryn A. O’Donnell,Erik A. Wentzel,Chrystal L. Montgomery,Hun‐Way Hwang,Tsung Cheng Chang,Perumal Vivekanandan,Michael Torbenson,K. Reed Clark,Jerry R. Mendell,Joshua T. Mendell
出处
期刊:Cell
[Elsevier]
日期:2009-06-01
卷期号:137 (6): 1005-1017
被引量:1589
标识
DOI:10.1016/j.cell.2009.04.021
摘要
Therapeutic strategies based on modulation of microRNA (miRNA) activity hold great promise due to the ability of these small RNAs to potently influence cellular behavior. In this study, we investigated the efficacy of a miRNA replacement therapy for liver cancer. We demonstrate that hepatocellular carcinoma (HCC) cells exhibit reduced expression of miR-26a, a miRNA that is normally expressed at high levels in diverse tissues. Expression of this miRNA in liver cancer cells in vitro induces cell-cycle arrest associated with direct targeting of cyclins D2 and E2. Systemic administration of this miRNA in a mouse model of HCC using adeno-associated virus (AAV) results in inhibition of cancer cell proliferation, induction of tumor-specific apoptosis, and dramatic protection from disease progression without toxicity. These findings suggest that delivery of miRNAs that are highly expressed and therefore tolerated in normal tissues but lost in disease cells may provide a general strategy for miRNA replacement therapies.
科研通智能强力驱动
Strongly Powered by AbleSci AI