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
Citations
More filters
Journal ArticleDOI
Insights into Biological Role of LncRNAs in Epithelial-Mesenchymal Transition.
Jun-Ting Cheng,Lingzhi Wang,Hong Wang,Feng Ru Tang,Wen-Qi Cai,Gautam Sethi,Hong-Wu Xin,Zhaowu Ma +7 more
TL;DR: Recent findings on the mechanisms and roles of lncRNAs in EMT are summarized and elaborate on how lnc RNAs can modulate EMT by interacting with RNA, DNA, or proteins in epigenetic, transcriptional, and post-transcriptional regulation.
Journal ArticleDOI
Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy.
Meng Wang,Dong Han,Ziming Yuan,Hanqing Hu,Zhixun Zhao,Runkun Yang,Yinghu Jin,Chaoxia Zou,Yinggang Chen,Guiyu Wang,Xu Gao,Xishan Wang,Xishan Wang +12 more
TL;DR: This study suggests that H19 mediates 5-Fu resistance in CRC via SIRT1 mediated autophagy, providing a novel mechanistic role of H19 in CRC chemoresistance, suggesting that H 19 may function as a marker for prediction of chemotherapeutic response to 5- Fu.
Journal ArticleDOI
Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma: implications for tumorigenesis, disease progression, and liver cancer stem cells.
Xiaoqi Huo,Shuanglin Han,Shuanglin Han,Guang Wu,Olivier Latchoumanin,Gang Zhou,Lionel Hebbard,Jacob George,Liang Qiao +8 more
TL;DR: A review summarizes data recently reported lncRNAs that might be critical for the maintenance of the biological properties of LCSCs, and some of which are closely linked to key aspects of liver cancer pathology, progression, outcomes and for thetenance of cancer stem cell-like properties.
Journal ArticleDOI
HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1/CDK2 signaling.
Jiaojiao Hu,Wei Song,Shaodan Zhang,Xiaohui Shen,Xuemei Qiu,Huazhang Wu,Pihai Gong,Sen Lu,Zhujiang Zhao,Ming-Liang He,Fan Hong +10 more
TL;DR: The findings demonstrate an important mechanism of hepatocarcinogenesis through the signaling of HBx-UCA1/EZH2-p27Kip1 axis, and a potential target of HCC.
Journal ArticleDOI
lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy
TL;DR: It is concluded that H19 regulates EndMT in diabetic retinopathy through specific mechanisms, which appear to involve TGF-β through a Smad-independent mechanism.
References
More filters
Journal ArticleDOI
Evolution and functions of long noncoding RNAs
TL;DR: The evolution of long noncoding RNAs and their roles in transcriptional regulation, epigenetic gene regulation, and disease are reviewed.
Journal ArticleDOI
Estimating the world cancer burden: Globocan 2000
TL;DR: GLOBOCAN 2000 updates the previous data-based global estimates of incidence, mortality and prevalence to the year 2000 and uses a “databased” approach, rather different from themodeling method used in other estimates.
Journal ArticleDOI
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Miao-Chih Tsai,Ohad Manor,Yue Wan,Nima Mosammaparast,Jordon K. Wang,Fei Lan,Yang Shi,Eran Segal,Howard Y. Chang +8 more
TL;DR: The results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
Journal ArticleDOI
Modular regulatory principles of large non-coding RNAs
TL;DR: This work synthesizes studies to provide an emerging model whereby large ncRNAs might achieve regulatory specificity through modularity, assembling diverse combinations of proteins and possibly RNA and DNA interactions.
Journal ArticleDOI
lincRNAs act in the circuitry controlling pluripotency and differentiation
Mitchell Guttman,Julie Donaghey,Bryce W. Carey,Manuel Garber,Jennifer K. Grenier,Glen Munson,Geneva Young,Anne Bergstrom Lucas,Robert A. Ach,Laurakay Bruhn,Xiaoping Yang,Ido Amit,Alexander Meissner,Alexander Meissner,Aviv Regev,Aviv Regev,John L. Rinn,John L. Rinn,David E. Root,Eric S. Lander,Eric S. Lander,Eric S. Lander +21 more
TL;DR: It is shown that Knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators.