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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Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma: dysregulation and implications for early detection, diagnosis and therapy.
Weihong Hou,Herbert L. Bonkovsky +1 more
TL;DR: Recent studies of non-coding RNAs, especially miRNAs and lncRNAs related to HCV-induced HCC are focused on, including those ncRNAs aberrantly expressed inHCV-associated HCC and the potential uses of nc RNAs in early detection, diagnosis and therapy of HCv- associated HCC.
Journal ArticleDOI
Coding-noncoding gene expression in intrahepatic cholangiocarcinoma
Jianguo Wang,Haiyang Xie,Qi Ling,Di Lu,Zhen Lv,Runzhou Zhuang,Zhikun Liu,Xuyong Wei,Lin Zhou,Xiao Xu,Shusen Zheng +10 more
TL;DR: In this article, the authors performed transcriptomic profiling of intrahepatic cholangiocarcinoma (ICC) and paired adjacent noncancerous tissues (N) by using lncRNA and messenger RNA (mRNA) microarrays.
Journal ArticleDOI
Long Non-Coding RNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Regulation, Functions, and Underlying Mechanisms.
TL;DR: This review briefly outlines recent findings of differentially expressed lncRNAs in HBV-related HCC, with particular focus on several key lnc RNAs, and discusses their regulation by HBV/HBx, their functions, and their underlying molecular mechanisms in the progression of HCC.
Journal ArticleDOI
Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: Recent progress and future prospects (Review)
TL;DR: The characteristics and biological roles of ncRNAs and their regulatory processes are important factors in liver tumorigenesis and potential therapeutic applications of n cRNAs in HCC are evaluated.
Journal ArticleDOI
Identification of important long non-coding RNAs and highly recurrent aberrant alternative splicing events in hepatocellular carcinoma through integrative analysis of multiple RNA-Seq datasets
TL;DR: Uncharacterized aspects of HCC transcriptome are revealed and important lncRNAs and splicing isoforms with the potential to serve as biomarkers and therapeutic targets for the disease are identified.
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