| An HNF4α-miRNA Inflammatory Feedback Circuit Regulates Hepatocellular Oncogenesis. | |
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MedLine Citation:
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PMID: 22153071 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Hepatocyte nuclear factor 4α (HNF4α) is essential for liver development and hepatocyte function. Here, we show that transient inhibition of HNF4α initiates hepatocellular transformation through a microRNA-inflammatory feedback loop circuit consisting of miR-124, IL6R, STAT3, miR-24, and miR-629. Moreover, we show that, once this circuit is activated, it maintains suppression of HNF4α and sustains oncogenesis. Systemic administration of miR-124, which modulates inflammatory signaling, prevents and suppresses hepatocellular carcinogenesis by inducing tumor-specific apoptosis without toxic side effects. As we also show that this HNF4α circuit is perturbed in human hepatocellular carcinomas, our data raise the possibility that manipulation of this microRNA feedback-inflammatory loop has therapeutic potential for treating liver cancer. |
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Authors:
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Maria Hatziapostolou; Christos Polytarchou; Eleni Aggelidou; Alexandra Drakaki; George A Poultsides; Savina A Jaeger; Hisanobu Ogata; Michael Karin; Kevin Struhl; Margarita Hadzopoulou-Cladaras; Dimitrios Iliopoulos |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cell Volume: 147 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1233-47 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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