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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DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts
Maria D. Paraskevopoulou,Maria D. Paraskevopoulou,Ioannis S. Vlachos,Dimitra Karagkouni,Georgios Georgakilas,Ilias Kanellos,Thanasis Vergoulis,Konstantinos Zagganas,Panayiotis Tsanakas,Evangelos Floros,Theodore Dalamagas,Artemis G. Hatzigeorgiou,Artemis G. Hatzigeorgiou +12 more
TL;DR: LncBase v2 hosts in silico predicted miRNA targets on lncRNAs, identified with the DIANA-microT algorithm, and caters information regarding cell type specific miRNA:lncRNA regulation and enables users to easily identify interactions in 66 different cell types, spanning 36 tissues for human and mouse.
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Long non-coding RNAs and complex diseases: from experimental results to computational models
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The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory
TL;DR: The growing evidence of H19’s involvement in both proliferation and differentiation processes, together with its involvement in epithelial to mesenchymal transition (EMT), has led to the conclusion that some of the recent disputes and discrepancies arising from current research findings can be resolved from a viewpoint supporting the oncogenic properties of H 19.
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Long non-coding RNA: a new player in cancer
TL;DR: Recent progress on the mechanisms and functions of lncRNAs in cancer are summarized, especially focusing on the oncogenic and tumor suppressive roles of the newly identified lnc RNAs, and the pathways these novel molecules might be involved in.
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Long noncoding RNAs: Novel insights into hepatocelluar carcinoma
TL;DR: The regulation and functional role of lncRNAs in HCC is discussed and the potential of lNCRNAs as prospective novel therapeutic targets in H CC is evaluated.
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