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https://www.readbyqxmd.com/read/29144570/lncapc-drives-wnt-%C3%AE-catenin-activation-and-liver-tic-self-renewal-through-ezh2-mediated-apc-transcriptional-inhibition
#1
Xiaomin Fu, Jizhen Lin, Fujun Qin, Zihe Yang, Yuechao Ding, Yong Zhang, Lu Han, Xiaoyan Zhu, Qinxian Zhang
Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling...
November 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29113254/epigenetic-analysis-of-fhl1-tumor-suppressor-gene-in-human-liver-cancer
#2
Jun Wang, Fang Huang, Jian Huang, Jindan Kong, Shenglan Liu, Jun Jin
Liver cancer is one of the most common types of cancer among human malignancies. Four and a half LIM domains 1 (FHL1), as a tumor suppressor gene, is frequently downregulated in multiple types of human cancer. However, the role and specific mechanisms of FHL1 as a tumor suppressor in liver cancer are poorly understood. The present study aimed to investigate the role and associated mechanisms of FHL1 in human liver cancer. The level of FHL1 mRNA in hepatocellular carcinoma (HCC) tissue specimens and cell lines derived from the human liver was determined using reverse transcription polymerase chain reaction and western blot analysis...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29106960/carnosol-mediated-sirtuin-1-activation-inhibits-enhancer-of-zeste-homolog-2-to-attenuate-liver-fibrosis
#3
Huanyu Zhao, Zhecheng Wang, Fan Tang, Yan Zhao, Dongcheng Feng, Yang Li, Yan Hu, Chao Wang, Junjun Zhou, Xiaofeng Tian, Jihong Yao
Quiescent hepatic stellate cell (HSC) activation and subsequent conversion into myofibroblasts is the central event in hepatic fibrosis pathogenesis. Epithelial - mesenchymal transition (EMT), another vital participant in liver fibrosis, has the potential to initiate HSC activation, which promotes abundant myofibroblast production. Previous studies suggest that Enhancer of Zeste Homolog 2 (EZH2) plays a significant role in myofibroblast transdifferentiation; however, the underlying mechanisms remain largely unaddressed...
October 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28970250/sirt1-antagonizes-liver-fibrosis-by-blocking-hepatic-stellate-cell-activation-in-mice
#4
Min Li, Wenxuan Hong, Chenzhi Hao, Luyang Li, Dongmei Wu, Aiguo Shen, Jun Lu, Yuanlin Zheng, Ping Li, Yong Xu
Hepatic stellate cells (HSCs) are a major source of fibrogenesis in the liver contributing to cirrhosis. When activated, HSCs transdifferentiate into myofibroblast and undergo profound functional alterations paralleling an overhaul of the transcriptome, the mechanism of which remains largely undefined. We investigated the involvement of the class III deacetylase sirtuin (silent information regulator 1, SIRT1) in HSC activation and liver fibrosis. SIRT1 levels were down-regulated in the livers in mouse models of liver fibrosis, in patients with cirrhosis, and in activated HSCs as opposed to quiescent HSCs...
September 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28939663/hepatoma-intrinsic-ccrk-inhibition-diminishes-myeloid-derived-suppressor-cell-immunosuppression-and-enhances-immune-checkpoint-blockade-efficacy
#5
Jingying Zhou, Man Liu, Hanyong Sun, Yu Feng, Liangliang Xu, Anthony W H Chan, Joanna H Tong, John Wong, Charing Ching Ning Chong, Paul B S Lai, Hector Kwong-Sang Wang, Shun-Wa Tsang, Tyler Goodwin, Rihe Liu, Leaf Huang, Zhiwei Chen, Joseph Jy Sung, King Lau Chow, Ka Fai To, Alfred Sze-Lok Cheng
OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) contribute to tumour immunosuppressive microenvironment and immune-checkpoint blockade resistance. Emerging evidence highlights the pivotal functions of cyclin-dependent kinases (CDKs) in tumour immunity. Here we elucidated the role of tumour-intrinsic CDK20, or cell cycle-related kinase (CCRK) on immunosuppression in hepatocellular carcinoma (HCC). DESIGN: Immunosuppression of MDSCs derived from patients with HCC and relationship with CCRK were determined by flow cytometry, expression analyses and co-culture systems...
September 22, 2017: Gut
https://www.readbyqxmd.com/read/28881044/from-large-to-small-the-immunohistochemical-panel-in-the-diagnosis-of-early-hepatocellular-carcinoma
#6
Francesco Vasuri, Deborah Malvi, Sonia Bonora, Silvia Fittipaldi, Matteo Renzulli, Francesco Tovoli, Rita Golfieri, Luigi Bolondi, Antonia D'Errico
AIMS: (i) to validate the immunohistochemical (IHC) markers Glutamine Synthetase (GS), Glypican-3 (GPC3), Heat Shock Protein-70 (HSP70) and Enhancer of Zeste homologue 2 (EZH2) on liver biopsy for the differential diagnosis between small HCC and non-neoplastic liver nodules, with special attention on <1 cm nodules; (ii) to assess the actual sensitivity and specificity of the single markers, and their combination, on needle biopsies. METHODS AND RESULTS: One-hundred (100) liver nodules, 66 HCC and 34 non-neoplastic nodules, were prospectively collected from 43 consecutive OLT patients, and subjected to "backtable" needle biopsies directly on surgical specimen...
September 7, 2017: Histopathology
https://www.readbyqxmd.com/read/28846110/hepatitis-b-virus-x-protein-promotes-the-development-of-liver-fibrosis-and-hepatoma-through-downregulation-of-mir-30e-targeting-p4ha2-mrna
#7
G X Feng, J Li, Z Yang, S Q Zhang, Y X Liu, W Y Zhang, L H Ye, X D Zhang
Hepatitis B virus (HBV)-induced liver necrosis takes great part in liver cirrhosis progression. However, less is known about whether hepatitis B virus X protein (HBx) has effect on liver fibrosis. Here, we report that HBV leads to liver fibrosis and hepatocarcinogenesis through miR-30e targeting P4HA2. HBV transgenic mouse was treated by CCl4 to generate a model of liver fibrosis. A crucial enzyme catalyzing collagen formation, prolyl 4-hydroxylase subunit α2 (P4HA2) was evaluated by immunohistochemistry, western blotting or quantitative reverse transcription-PCR analysis...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28810927/stat3-mediated-upregulation-of-lncrna-hoxd-as1-as-a-cerna-facilitates-liver-cancer-metastasis-by-regulating-sox4
#8
Hui Wang, Xisong Huo, Xin-Rong Yang, Jia He, Lijun Cheng, Na Wang, Xuan Deng, Haojie Jin, Ning Wang, Cun Wang, Fangyu Zhao, Jingyuan Fang, Ming Yao, Jia Fan, Wenxin Qin
BACKGROUND: Several of the thousands of human long noncoding RNAs (lncRNAs) have been functionally characterized, yet their potential involvement in hepatocellular carcinoma (HCC) remains poorly understood. METHODS: LncRNA-HOXD-AS1 was identified by microarray and validated by real-time PCR. The clinicopathological significance of HOXD-AS1 was analyzed by Kaplan-Meier method. Chromatin immunoprecipitation was conducted to examine the mechanism of HOXD-AS1 upregulation...
August 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28548121/ebv-negative-aggressive-nk-cell-leukemia-lymphoma-a-clinical-and-pathological-study-from-a-single-institution
#9
Juehua Gao, Amir Behdad, Peng Ji, Kristy L Wolniak, Olga Frankfurt, Yi-Hua Chen
Aggressive natural killer (NK)-cell leukemia/lymphoma is a systemic NK-cell neoplasm that preferentially affects Asians with a fulminant clinical course and is almost always associated with Epstein-Barr virus (EBV). The data on EBV-negative aggressive NK-cell leukemia/lymphoma are limited. Here we report a series of three patients (two Caucasians, one African-American) with EBV-negative aggressive NK-cell leukemia/lymphoma from a single institution, including a case diagnosed on post-mortem examination. Similar to EBV-positive aggressive NK-cell leukemia/lymphoma, our patients presented with constitutional symptoms and hepatosplenomegaly, and followed a highly aggressive clinical course...
August 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28529687/histone-demethylases-utx-and-jmjd3-are-required-for-nkt-cell-development-in-mice
#10
Daniel Northrup, Ryoji Yagi, Kairong Cui, William R Proctor, Chaochen Wang, Katarzyna Placek, Lance R Pohl, Rongfu Wang, Kai Ge, Jinfang Zhu, Keji Zhao
BACKGROUND: Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. RESULTS: We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28338656/focal-adhesion-kinase-depletion-reduces-human-hepatocellular-carcinoma-growth-by-repressing-enhancer-of-zeste-homolog-2
#11
Daniela Gnani, Ilaria Romito, Simona Artuso, Marco Chierici, Cristiano De Stefanis, Nadia Panera, Annalisa Crudele, Sara Ceccarelli, Elena Carcarino, Valentina D'Oria, Manuela Porru, Ezio Giorda, Karin Ferrari, Luca Miele, Erica Villa, Clara Balsano, Diego Pasini, Cesare Furlanello, Franco Locatelli, Valerio Nobili, Rossella Rota, Carlo Leonetti, Anna Alisi
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes...
May 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28332284/ezh2-mediated-repression-of-dkk1-promotes-hepatic-stellate-cell-activation-and-hepatic-fibrosis
#12
Yang Yang, Xiao-Xia Chen, Wan-Xia Li, Xiao-Qin Wu, Cheng Huang, Juan Xie, Yu-Xin Zhao, Xiao-Ming Meng, Jun Li
EZH2, a histone H3 lysine-27-specific methyltransferase, is involved in diverse physiological and pathological processes including cell proliferation and differentiation. However, the role of EZH2 in liver fibrosis is largely unknown. In this study, it was identified that EZH2 promoted Wnt pathway-stimulated fibroblasts in vitro and in vivo by repressing Dkk-1, which is a Wnt pathway antagonist. The expression of EZH2 was increased in CCl4 -induced rat liver and primary HSCs as well as TGF-β1-treated HSC-T6, whereas the expression of Dkk1 was reduced...
October 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28328977/jmjd3-aids-in-reprogramming-of-bone-marrow-progenitor-cells-to-hepatic-phenotype-through-epigenetic-activation-of-hepatic-transcription-factors
#13
Veena Kochat, Zaffar Equbal, Prakash Baligar, Vikash Kumar, Madhulika Srivastava, Asok Mukhopadhyay
The strictly regulated unidirectional differentiation program in some somatic stem/progenitor cells has been found to be modified in the ectopic site (tissue) undergoing regeneration. In these cases, the lineage barrier is crossed by either heterotypic cell fusion or direct differentiation. Though studies have shown the role of coordinated genetic and epigenetic mechanisms in cellular development and differentiation, how the lineage fate of adult bone marrow progenitor cells (BMPCs) is reprogrammed during liver regeneration and whether this lineage switch is stably maintained are not clearly understood...
2017: PloS One
https://www.readbyqxmd.com/read/28177890/long-noncoding-rna-hotair-promotes-metastasis-of-renal-cell-carcinoma-by-up-regulating-histone-h3k27-demethylase-jmjd3
#14
Ming Xia, Lv Yao, Qiaoxia Zhang, Feng Wang, Hongbin Mei, Xiaoqiang Guo, Weiren Huang
Long Noncoding RNAs (lncRNAs) are a kind of non-protein coding transcripts longer than 200 nucleotides, and play important roles in diverse biological processes, such as embryonic development and apoptosis. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) is a negative prognostic factor in a variety of human cancers, such as breast, liver and lung cancers. HOTAIR can promote cancer cell metastasis by reprogramming chromatin organization. In the present study, HOTAIR expression was elevated in tissues of renal cell carcinoma compared to adjacent normal tissues, and positively correlated with metastasis (P<0...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27721404/a-pre-neoplastic-epigenetic-field-defect-in-hcv-infected-liver-at-transcription-factor-binding-sites-and-polycomb-targets
#15
N A Wijetunga, M Pascual, J Tozour, F Delahaye, M Alani, M Adeyeye, A W Wolkoff, A Verma, J M Greally
The predisposition of patients with Hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) involves components of viral infection, inflammation and time. The development of multifocal, genetically distinct tumours is suggestive of a field defect affecting the entire liver. The molecular susceptibility mediating such a field defect is not understood. One potential mediator of long-term cellular reprogramming is heritable (epigenetic) regulation of transcription, exemplified by DNA methylation. We studied epigenetic and transcriptional changes in HCV-infected livers in comparison with control, uninfected livers and HCC, allowing us to identify pre-neoplastic epigenetic and transcriptional events...
April 6, 2017: Oncogene
https://www.readbyqxmd.com/read/27690696/modified-adenovirus-reduces-de-novo-peritoneal-adhesions-in-rats-and-limits-off-target-transfection-role-of-ezh2-in-adhesion-formation
#16
Hussein M Atta, Ayman A Al-Hendy, Salama R Abdel Raheim, Hend Abdel-Ghany, Khalid A Nasif, Ahlam M Abdellah, Nagwa M Zenhom, Heba S Kamel
AIM OF THE STUDY: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. MATERIALS AND METHODS: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions...
April 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/27367027/inflammatory-related-gene-ikk%C3%AE-ikk%C3%AE-ikk%C3%AE-cooperates-to-determine-liver-cancer-stem-cells-progression-by-altering-telomere-via-heterochromatin-protein-1-hotair-axis
#17
Jiahui An, Mengying Wu, Xiaoru Xin, Zhuojia Lin, Xiaonan Li, Qidi Zheng, Xin Gui, Tianming Li, Hu Pu, Haiyan Li, Dongdong Lu
Cancer stem cells are associated with tumor recurrence. IKK is a protein kinase that is composed of IKKα, IKKβ, IKKγ. Herein, we demonstrate that IKKα plus IKKβ promoted and IKKγ inhibited liver cancer stem cell growth in vitro and in vivo. Mechanistically, IKKα plus IKKβ enhanced and IKKγ inhibited the interplay among HP1α, HP1β and HP1γ that competes for the interaction among HP1α, SUZ12, HEZ2. Therefore, IKKα plus IKKβ inhibited and IKKγ enhanced the activity of H3K27 methyltransferase SUZ12 and EZH2, which methylates H3K27 immediately sites on HOTAIR promoter region...
August 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27239797/lnc-%C3%AE-catm-elicits-ezh2-dependent-%C3%AE-catenin-stabilization-and-sustains-liver-csc-self-renewal
#18
Pingping Zhu, Yanying Wang, Guanling Huang, Buqing Ye, Benyu Liu, Jiayi Wu, Ying Du, Lei He, Zusen Fan
Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC); however, the molecular mechanisms underlying their self-renewal and differentiation remain largely unknown. Through analysis of transcriptome microarray data, we identified a long noncoding RNA (lncRNA) called lnc-β-Catm, which is highly expressed in human HCC tumors and liver CSCs. We found that lnc-β-Catm is required for self-renewal of liver CSCs and tumor propagation in mice...
July 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27145952/normal-formation-of-a-vertebrate-body-plan-and-loss-of-tissue-maintenance-in-the-absence-of-ezh2
#19
Bilge San, Naomi D Chrispijn, Nadine Wittkopp, Simon J van Heeringen, Anne K Lagendijk, Marco Aben, Jeroen Bakkers, René F Ketting, Leonie M Kamminga
Polycomb group (PcG) proteins are transcriptional repressors of numerous genes, many of which regulate cell cycle progression or developmental processes. We used zebrafish to study Enhancer of zeste homolog 2 (Ezh2), the PcG protein responsible for placing the transcriptional repressive H3K27me3 mark. We identified a nonsense mutant of ezh2 and generated maternal zygotic (MZ) ezh2 mutant embryos. In contrast to knockout mice for PcG proteins, MZezh2 mutant embryos gastrulate seemingly normal, but die around 2 days post fertilization displaying pleiotropic phenotypes...
May 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26848027/enhancer-of-zeste-homolog-2-depletion-arrests-the-proliferation-of-hepatoblastoma-cells
#20
Yue Wang, Yongtao Xiao, Kai Chen, Sheng Chen, Min Zhang, Zhixiang Wu, Yeming Wu
Hepatoblastoma is the most common type of malignant liver tumor in children. While outcomes have been greatly improved in the past decades, the treatment of advanced hepatoblastoma has remained challenging. Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group regulators of gene activity, is amplified and overexpressed in a variety of cancers. However, the role of EZH2 in hepatoblastoma has remained to be fully elucidated. The purpose of the present study was to investigate the expression patterns of EZH2 in hepatoblastoma cells and to assess the anti‑cancer effects of EZH2 depletion...
March 2016: Molecular Medicine Reports
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