Detailed Instructions: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
Problem:Context: Hepatocyte nuclear factor 4 (HNF4) is a liver enriched transcription factor and is indispensable for liver development. However, the role of HNF4 in hepatocellular carcinoma (HCC) progression remains to be elucidated. We report that reduced HNF4 expression correlated well with the aggressive clinicopathological characteristics of HCC and predicted poor prognosis of patients. HNF4 levels were even lower in metastatic HCCs, and ectopic HNF4 expression suppressed the metastasis of hepatoma cells both in vitro and in vivo. Forced HNF4 expression attenuated the expression and nuclear translocation of RelA (p65) and impaired NF-B activation through an IKK-independent mechanism. Blockage of RelA robustly attenuated the suppressive effect of HNF4 on hepatoma cell metastasis. MicroRNA (miR)-7 and miR-124 were transcriptionally up-regulated by HNF4, which repressed RelA expression by way of interaction with RelA-3' untranslated region (UTR). In addition, nuclear factor kappa B (NF-B) up-regulated the expression of miR-21 in hepatoma cells, resulting in decreased HNF4 levels through down-regulating HNF4-3'UTR activity.
Answer: Collectively, an HNF4-NF-B feedback circuit including miR-124, miR-7, and miR-21 was identified in HCC, and the combination of HNF4 and NF-B exhibited more powerful predictive efficiency of patient prognosis. These findings broaden the knowledge of hepatic inflammation and cancer initiation/progression, and also provide novel prognostic biomarkers and therapeutic targets for HCC.
Solution:
Does hepatocyte nuclear factor 4-nuclear factor-B feedback circuit modulate liver cancer progression?