Hepatocyte nuclear factor-4α reverses malignancy of hepatocellular carcinoma through regulating miR-134 in the DLK1-DIO3 region

• DOI: 10.1002/hep.26573
• Publication Date: 2013-06-14T16:11:50Z
• Authors: Chuan Yin; Pei-Qin Wang; Wen-Ping Xu; Yuan Yang; Qing Zhang; Bei-Fang Ning; Ping-Ping Zhang; Wei-Ping Zhou; Wei-Fen Xie; Wan-Sheng Chen; Xin Zhang
• Keywords: Hepatocyte nuclear factors; HCCS

Hepatocyte nuclear factor-4α (HNF4α) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis. There striking suppression carcinoma (HCC) by HNF4α, although the mechanisms which HNF4α reverses HCC malignancy are largely unknown. Herein, we demonstrate that administration to cells resulted in elevated levels 28 mature microRNAs (miRNAs) from miR-379-656 cluster, located delta-like 1 homolog (DLK1) -iodothyronine deiodinase 3 (DIO3) locus on human chromosome 14q32. Consistent with reduction these miRNAs were down-regulated tissue. regulated transcription cluster directly binding its response element DLK1-DIO3 region. Interestingly, several this inhibited proliferation metastasis vitro. As representative miRNA miR-134 exerted dramatically suppressive effect down-regulating oncoprotein, KRAS. Moreover, markedly diminished tumorigenicity displayed significant antitumor vivo. In addition, inhibition endogenous partially reversed effects KRAS expression malignancy. Furthermore, positive correlation between was observed during hepatocarcinogenesis rats, decreases significantly associated aggressive behavior HCCs. Conclusion: Our data highlight importance inhibitory HCC, suggest regulation HNF4α-miRNA cascade may have beneficial treatment HCC. (Hepatology 2013; 58:1964–1976)