Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma
Ling Zhang,Fu Yang,Ji-hang Yuan,Sheng-xian Yuan,Weiping Zhou,Xi-song Huo,Dan Xu,Hai-shan Bi,Fang Wang,Shuhan Sun +9 more
TLDR
It is shown that H19 was underexpressed in intratumoral HCC tissues (T), as compared with peritumoral tissues (L), and low T/L ratio of H19 predicted poor prognosis, which could suggest the development of combination therapies that target H19 and the miR-200 family.Abstract:
Although numerous long non-coding RNAs (lncRNAs) have been identified in mammals, many of their biological roles remain to be characterized. Early reports suggest that H19 contributes to carcinogenesis, including hepatocellular carcinoma (HCC). Examination of the Oncomine resource showed that most HCC cases express H19 at a level that is comparable with the liver, with a tendency toward lower expression. This is consistent with our previous microarray data and indicates a more complicated role of H19 in HCC that needs to be characterized. In this study, the expression level of H19 was assessed in different regions of HCC patients' liver samples. Loss- and gain-of-function studies on this lncRNA in the HCC cell lines, SMMC7721 and HCCLM3, were used to characterize its effects on gene expression and to assess its effect on HCC metastasis both in vitro and in vivo. In this study, we show that H19 was underexpressed in intratumoral HCC tissues (T), as compared with peritumoral tissues (L). Additionally, low T/L ratio of H19 predicted poor prognosis. H19 suppressed HCC progression metastasis and the expression of markers of epithelial-to-mesenchymal transition. Furthermore, H19 associated with the protein complex hnRNP U/PCAF/RNAPol II, activating miR-200 family by increasing histone acetylation. The results demonstrate that H19 can alter the miR-200 pathway, thus contributing to mesenchymal-to-epithelial transition and to the suppression of tumor metastasis. These data provide an explanation for the hitherto puzzling literature on the relationship between H19 and cancer, and could suggest the development of combination therapies that target H19 and the miR-200 family.read more
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Epigenetic Regulation in Hepatocellular Carcinoma Requires Long Noncoding RNAs
TL;DR: The evidence presented in this review highlights that lncRNAs-mediated epigenetic regulation should be taken into account for potential targeted therapeutic approaches.
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Sex Differences in the Methylome and Transcriptome of the Human Liver and Circulating HDL-Cholesterol Levels.
Sonia García-Calzón,Alexander Perfilyev,Vanessa D. de Mello,Jussi Pihlajamäki,Charlotte Ling +4 more
TL;DR: Human liver has a sex-specific methylation profile in both the X-chromosome and autosomes, which associates with hepatic gene expression changes and HDL-cholesterol, and KDM6A is identified as a novel target that regulates HDL- cholesterol levels.
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Missing Links in Epithelial-Mesenchymal Transition: Long Non-Coding RNAs Enter the Arena.
TL;DR: Understanding the different and precise molecular mechanisms by which functional lncRNAs switch EMT on and off is important for opening up new avenues in lncRNA-directed diagnosis, prognosis, and therapeutic intervention against cancer.
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Epigenetically silenced long noncoding-SRHC promotes proliferation of hepatocellular carcinoma.
Hao Zheng,Sen Yang,Yuan Yang,Sheng-xian Yuan,Fu-Quan Wu,Li-Li Wang,Hong-Li Yan,Shuhan Sun,Weiping Zhou +8 more
TL;DR: A new long noncoding RNA designated as SRHC is identified that is capable of inhibiting cancer proliferation and is down-regulated in tumors at least partly by DNA methylation.
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The role of long non-coding RNAs in hepatitis B virus-related hepatocellular carcinoma.
TL;DR: Their involvement in viral replication, the specific association of certain lncRNAs with HBV-related HCC, potential utility as therapeutic targets and diagnostic markers are discussed.
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