Interestingly, miR-125b level was found to be inversely correlated with SUV39H1 expression (P = 0.001) in clinical Selleckchem MI-503 specimens. Our observations suggested that miR-125b down-regulation may account for the aberrant SUV39H1 level in HCC. Conclusion: Our study demonstrated that SUV39H1 up-regulation contributed to HCC development and metastasis. The tumor-suppressive miR-125b served as a negative regulator of SUV39H1. (HEPATOLOGY 2013) Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide and ranks as the third leading cause of cancer-related death. HCC is highly
heterogeneous and develops through complex multistep processes that are accompanied
by the acquisition of various molecular abnormalities.1,2 In addition to genetic alterations, such as chromosomal deletion and gene mutation, epigenetic dysregulation has been evidently demonstrated as a key event in liver cancer pathogenesis. Epigenetic regulation generally refers to the changes in DNA methylation and histone modification pattern that modify gene transcription STA-9090 without affecting DNA sequence.3 Aberrant DNA hypermethylation in HCC has been frequently observed on promoter regions and accounts for the underexpression of tumor-suppressor genes, such as cyclin-dependent kinase inhibitor p16/INK4A,4,5 E-cadherin,6 phosphate and tensin homolog (PTEN),7 deleted in liver cancer 1 (DLC1),8 and tissue factor pathway inhibitor 2 (TFPI-2).9 Apart from DNA methylation, deregulated histone methylation has gained recent recognition
as another important epigenetic alteration in carcinogenesis. Histone methylation critically determines chromosomal structure and stability, as well as the accessibility of the transcription factor. Global changes in histone methylation have been associated with tumor recurrence and patient survival in prostate cancer,10,11 non-small-cell lung cancer,12,13 bladder cancer,14 squamous-cell carcinoma of the esophagus,15 and colorectal cancer.16 The frequently observed changes of histone methylation pattern in human cancers may attribute to the deregulation of upstream histone methyltransferases. For instance, our recent study MCE demonstrated that the H3K27 methyltransferase, EZH2, and its associated polycomb repressive complex 2 members (EED, SUZ12, and RBBP7) were substantially up-regulated in human HCC and contributed to HCC metastasis by epigenetic silencing on multiple tumor-suppressive microRNAs (miRNAs). Interestingly, in addition to EZH2, we also observed a common up-regulation of SET-domain containing methyltransferases in primary human HCC, which highlighted the significance of histone methylation in liver carcinogenesis.