An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis

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

Research output: Contribution to journalArticlepeer-review

402 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1233-1247
Number of pages15
Issue number6
Publication statusPublished - Dec 9 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


Dive into the research topics of 'An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis'. Together they form a unique fingerprint.

Cite this