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Arresting the Culprit: Targeted Antagomir Delivery to Sequester Oncogenic miR-221 in HCC

Authors
Journal
Molecular Therapy — Nucleic Acids
2162-2531
Publisher
Nature Publishing Group
Publication Date
Volume
1
Issue
3
Identifiers
DOI: 10.1038/mtna.2012.2
Keywords
  • Commentary
Disciplines
  • Chemistry
  • Medicine

Abstract

Arresting the Culprit: Targeted Antagomir Delivery to Sequester Oncogenic miR-221 in HCC Citation: Molecular Therapy–Nucleic Acids (2012) 1, e12; doi:10.1038/mtna.2012.2 © 2012 American Society of Gene & Cell Therapy All rights reserved 2158-3188/11 www.nature.com/mtna 1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA Correspondence: Frank J Slack, Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520, USA. E-mail: [email protected] Various treatment options are available for hepatocellular carcinoma (HCC); however, the overwhelming majority of them fail to extend patient survival, especially in cases of advanced disease. Although a number of different genetic lesions have been linked to HCC, the expression of onco- genic microRNAs (miRNAs), such as miR-221 and miR-222, are consistently found elevated in HCC tumor specimens,1,2 suggesting that silencing of these miRNAs might slow or stop tumor growth. In a recent study, Park et al. show that systemic administration of a chemically modified oligonucle- otide that binds to and sequesters miR-221 is efficacious in HCC.3 Their approach identified a preferred chemical modifi- cation on the oligonucleotide that allowed its accumulation in hepatocytes, which led to therapeutic silencing of miR-221, reduced cellular proliferation, and most importantly increased survival of an orthotopic mouse model of HCC. Although this approach has yet to be tried in human patients, it appears likely that treatments involving miRNA overexpression or silencing, such as these, will translate efficiently. HCC is the fifth most prevalent cancer worldwide and the third most common cause of cancer-related deaths.4 Molecular markers of the disease include genetic instabil- ity, reexpression of telomerase reverse transcriptase, loss of cell-cycle checkpoint control, and inhibition of apoptotic signaling pathways, su

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