Hepatic Cell News Volume 3.09 | Mar 15 2019

TOP STORY

Lnc-UCID Promotes G1/S Transition and Hepatoma Growth by Preventing DHX9-Mediated CDK6 Downregulation

Investigators identified a novel oncogenic long noncoding RNA (lncRNA) and named it as lnc-UCID (lncRNA upregulating CDK6 by interacting with DHX9). Lnc-UCID was upregulated in hepatocellular carcinoma (HCC) and higher lnc-UCID level was correlated with shorter recurrence-free survival of HCC patients. Both gain- and loss-of function studies revealed that lnc-UCID enhanced CDK6 expression and thereby promoted G1/S transition and cell proliferation. [Hepatology] Abstract

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NAD(P)H: Quinone Oxidoreductase 1 Overexpression in Hepatocellular Carcinoma Potentiates Apoptosis Evasion through Regulating Stabilization of X-linked Inhibitor of Apoptosis Protein

Loss-of-function of NAD(P)H: quinone oxidoreductase 1 (NQO1) inhibited growth in hepatocellular carcinoma (HCC) cells with increased apoptosis in vitro, and suppressed orthotopic tumorigenicity in vivo. Mechanistically, high level of NQO1 in HCC cells enhanced protein stability of X-linked inhibitor of apoptosis protein by increasing its phosphorylation at Ser 87. [Cancer Lett] Abstract

The Methionine Salvage Pathway-Involving ADI1 Inhibits Hepatoma Growth by Epigenetically Altering Genes Expression via Elevating S-Adenosylmethionine

By altering acireductone dioxygenase 1 (ADI1) expression in hepatocellular carcinoma cells, a negative correlation between ADI1 and cell proliferation was observed. Cell-based and xenograft experiments were performed by using cells overexpressing ADI1 mutants carrying mutations at the metal-binding sites, which selectively disrupted differential catalytic steps, resulting in staying or leaving the 5′-methylthioadenosine cycle. [Cell Death Dis] Full Article

β-Thujaplicin Induces Autophagic Cell Death, Apoptosis, and Cell Cycle Arrest through ROS-Mediated Akt and p38/ERK MAPK Signaling in Human Hepatocellular Carcinoma

Scientists found that β-thujaplicin inhibits the growth of hepatocellular carcinoma cells, but not normal liver cells, with nanomolar potency. They found that β-thujaplicin could induce autophagy, as judged by Western blot, confocal microscopy, and transmission electron microscopy. [Cell Death Dis] Full Article

Novel Urokinase-Plasminogen Activator Inhibitor SPINK13 Inhibits Growth and Metastasis of Hepatocellular Carcinoma In Vivo

The expression of urokinase-plasminogen activator (uPA) was examined by quantitative polymerase chain reaction in hepatic cell lines. Protein interaction between uPA and SPINK13 was identified by immunoprecipitation. In vitro biochemical assay was used to examine the inhibitory effect of the SPINK13 on the direct cleaving of the recombinant pro-matrix metalloproteinases 9 by uPA. [Pharmacol Res] Abstract | Graphical Abstract

Spicatoside A Derived from Liriope platyphylla Root Ethanol Extract Inhibits Hepatitis E Virus Genotype 3 Replication In Vitro

Liriope platyphylla ethanol extract (LPE) suppressed replication of the genotype 3 hepatitis E virus (HEV) replicon. Sequential solvent fractionation revealed that the ethyl acetate (EA) fraction of LPE exerts the most potent inhibitory effects. With the aid of activity-guided fractionation and multi-step column chromatography, spicatoside A was subsequently isolated in the EA fraction of LPE and specifically shown to exert inhibitory effects on replication of the genotype 3 HEV replicon. [Sci Rep] Full Article

Hyaluronic Acid Inhibition by 4-Methylumbelliferone Reduces the Expression of Cancer Stem Cells Markers during Hepatocarcinogenesis

Researchers observed that 4-methylumbelliferone treatments in animal model down-regulated the mRNA expressions of hyaluronic acid (HA)-related genes Has3 and Hyal2 only in C57BL/6J-Tg(Alb1HBV)44Bri/J but not in normal C57BL/6-J. As observed in vivo, in hepatocellular carcinoma cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. [Sci Rep] Full Article

8-Bromo-7-Methoxychrysin Suppress Stemness of SMMC-7721 Cells Induced by Co-Culture of Liver Cancer Stem-Like Cells with Hepatic Stellate Cells

The second-generation spheres by sphere culture were identified and used as SMMC-7721-and MHCC97H-derived liver cancer stem-like cells (LCSLCs). SMMC-7721-and MHCC97-derived LCSCs/LX-2 cells transwell co-culture system was treated with 8-bromo-7-methoxychrysin and its lead compound chrysin. [BMC Cancer] Full Article

Hepatitis C Virus Core Protein Interacts with Cellular Metastasis Suppressor Nm23-H1 and Promotes Cell Migration and Invasion

Scientists showed that the core protein of hepatitis C virus (HCV) genotype 2a could co-localize and interacedt directly with Nm23-H1 within cancer cells, resulting in modulation of the anti-metastasis properties of Nm23-H1. The HCV core protein promoted SUMOylation and degradation of the Nm23-H1 protein, as well as transcriptional downregulation. [Arch Virol] Abstract

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Molecular Functions and Clinical Impact of Thyroid Hormone-Triggered Autophagy in Liver-Related Diseases

The authors review recent studies focusing on the involvement of thyroid hormones in hepatic homeostasis through induction of autophagy and their implications in liver-related diseases. [J Biomed Sci] Full Article

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STEMCELL Technologies Wins Deloitte Best Managed Companies Award

STEMCELL Technologies announced that the company has been selected as a winner of Canada’s Best Managed Companies program for 2019. Canada’s Best Managed Companies is the country’s leading business awards program, recognizing excellence in the management abilities and practices of Canadian owned and managed companies with revenues over $15 million. [STEMCELL Technologies, Inc.] Press Release

Galmed Reports Positive Results from Pharmacokinetic Split Dose Study of Aramchol

Galmed Pharmaceuticals Ltd. a clinical-stage biopharmaceutical company focused on the development of the liver targeted SCD1 modulator, Aramchol, an oral therapy for the treatment of nonalcoholic steatohepatitis and fibrosis, announced positive results from a pharmacokinetic study showing that dose splitting of Aramchol 600mg to twice daily 300mg significantly increased plasma levels. [Galmed Pharmaceuticals Ltd] Press Release

Lipocine’s LPCN 1144 for NASH Demonstrates Substantial Fatty Liver Resolution and Meaningful Liver Fat Reduction in NAFLD Population

Lipocine Inc. announced top-line results from the 16-week Liver Fat Imaging Study with LPCN 1144. [Lipocine Inc.] Press Release

Survey Highlights “Shocking” Gender Bias Among PI Pay in UK

Organizers of a survey of early-career scientists in the UK say they are shocked by the picture it paints of gender bias in British science. Women principal investigators (PIs) who have started their own lab in recent years are paid thousands of pounds a year less than men at the same stage of their career, the results show. [The Scientist] Editorial

Norway Joins List of Countries Canceling Elsevier Contracts

Norway has become latest country to cancel its contracts with Elsevier following a dispute over access to research papers. In a statement, the Norwegian Directorate for ICT and Joint Services in Higher Education and Research, which represents a consortium of research institutions in the country, rejected Elsevier’s offer to lower some of its costs for Norwegian institutions because it didn’t go far enough to promote free access to published research. [The Scientist] Editorial

NEW Obesity and NAFLD: Mechanisms and Therapeutics
February 23-27, 2020
Banff, Alberta, Canada

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NEW Professor/Associate Professor – Cancer Biology (Norwegian University of Science and Technology)

NEW Postdoctoral Position – Stem Cell Biology (University of Zurich)

Postdoctoral Position – Hepatitis C Virus Vaccine Research (TWINCORE – Centre for Experimental and Clinical Infection Research)

Postdoctoral Position – Non-Alcoholic Fatty Liver Disease (University of California, San Diego)

Assistant Professor – Computational Biology/Stem Cell Biology (University of Illinois at Chicago)

Postdoctoral Research Associate – Liver DIseases (University of Illinois at Chicago)

Senior Research Scientist – Nonalcoholic Steatohepatitis (Gilead Sciences, Inc)

Postdoctoral Research Scientist – Cancer Biology (The Beatson Institute for Cancer Research)

Assistant/Associate Professor – Cancer Biology (Virginia Commonwealth University)

Postdoctoral Researcher – Cancer Biology (University of California, San Francisco)

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