Hepatic Cell News Volume 3.26 | Jul 19 2019

TOP STORY

Defective HNF4alpha-Dependent Gene Expression as a Driver of Hepatocellular Failure in Alcoholic Hepatitis

TGFβ1 was a key upstream transcriptome regulator in alcoholic hepatitis (AH) and induced the use of HNF4α P2 promoter in hepatocytes, which resulted in defective metabolic and synthetic functions. Gene polymorphisms in liver-enriched transcription factors including HNF4α were not associated with the development of AH. [Nat Commun] Full Article

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Identification of a CIP4 PKA Phosphorylation Site Involved in the Regulation of Cancer Cell Invasiveness and Metastasis

Investigators identified CDC42 interacting protein 4 (CIP4) T225 as the major CIP4 A-kinase (PKA) phosphorylation site. In vitro and in vivo experiments using hepatocellular carcinoma and breast cancer cells showed that expression of a CIP4(T225E) phosphomimetic mutant increased cancer cell metastatic capacity and that, conversely, expression of a CIP4(T225A) non-phosphorylatable mutant reduced invasive properties. [Cancer Lett] Abstract

A miR-194/PTBP1/CCND3 Axis Regulates Tumor Growth in Human Hepatocellular Carcinoma

Investigators identified polypyrimidine tract-binding protein 1 (PTBP1) as a positive regulator of human hepatocellular carcinoma (HCC) growth. The expression of PTBP1 was increased in human HCC cells and tissues compared to the corresponding controls, and this high expression was positively correlated with increased tumor size and a reduced survival rate. [J Pathol] Abstract

Reversal of Sorafenib Resistance in Hepatocellular Carcinoma: Epigenetically Regulated Disruption of 14-3-3η/Hypoxia-Inducible Factor-1α

An analysis of the underlying molecular mechanisms revealed that 14-3-3η stabilizes hypoxia-inducible factor 1α (HIF-1α) through the inhibition of ubiquitin-dependent proteasome protein degradation, which led to the maintenance of cancer stem cell (CSC) properties. Researchers further found that microRNA-16 was a competent miRNA that reverses sorafenib resistance by targeting the 3′-UTR of 14-3-3η and thereby inhibited 14-3-3η/HIF-1α/CSC properties. [Cell Death Discov] Full Article

Therapeutic Effect of Yttrium Oxide Nanoparticles for the Treatment of Fulminant Hepatic Failure

Y₂O₃ nanoparticles (NPs) exhibited anti-inflammatory activity by scavenging cellular reactive oxygen species and dampening reactive oxygen species-mediated NF-κB activation in vitro. A single intraperitoneal administration of Y₂O₃ NPs enhanced hepatic antioxidant status and reduced oxidative stress and inflammatory response in lipopolysaccharide/galactosamine-induced mice. [Nanomedicine (Lond)] Abstract

Chemopreventive Effect of Phytosomal Curcumin on Hepatitis B Virus-Related Hepatocellular Carcinoma in a Transgenic Mouse Model

Phytosomal curcumin exerted considerably stronger effects on activation of anti-inflammatory PPARγ as well as inhibition of pro-inflammatory NF-κB than unformulated curcumin. Furthermore, phytosomal curcumin showed a comparable effect on suppression of oncogenic mTOR activation to unformulated curcumin. [Sci Rep] Full Article

Radiation-Induced CXCL12 Upregulation via Histone Modification at the Promoter in the Tumor Microenvironment of Hepatocellular Carcinoma

The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and co-culture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. [Mol Cells] Abstract

AEBP1 Expression Increases with Severity of Fibrosis in NASH and Is Regulated by Glucose, Palmitate, and miR-372-3p

AEBP1 expression was upregulated 5.8-fold in activated hepatic stellate cells and downregulated during chemical and contact induction of biological quiescence. In LX-2 and HepG2 cells treated with high glucose, AEBP1 expression increased over seven-fold compared to normal glucose conditions. [PLoS One] Full Article | Editorial

Three-Dimensional Cultured Liver-on-a-Chip with Mature Hepatocyte-Like Cells Derived from Human Pluripotent Stem Cells

Scientists developed a very simple liver-on-a-chip platform with mature and functional hepatocyte-like cells derived from human pluripotent stem cells (hPSCs). To establish a method for hepatic differentiation of hPSCs, cells were first treated by inhibiting the phosphoinositide 3-kinase- and Rho-associated protein kinase-signaling pathways to stop self-renewal and improve survival, respectively, which enabled the formation of a well-defined endoderm and facilitated hepatocyte commitment. [Biomed Microdevices] Abstract

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Liver Organoids: From Basic Research to Therapeutic Applications

While mouse models and cell lines have furthered our understanding of liver biology and associated diseases, they suffer in replicating key aspects of human liver tissue, in particular its complex architecture and metabolic functions. Liver organoids have now been established for multiple species from induced pluripotent stem cells, embryonic stem cells, hepatoblasts and adult tissue-derived cells. [Gut] Full Article

miRNAs and NAFLD: From Pathophysiology to Therapy

The authors discuss the recent progress addressing the role of the many facets of complex miRNA regulatory networks in the development and progression of non-alcoholic fatty liver disease (NAFLD). The basic concepts and mechanisms of miRNA-mediated gene regulation as well as the various setbacks encountered in basic and translational research in this field are debated. miRNAs identified so far, whose expressions/activities are deregulated in NAFLD, and which contribute to the outcomes of this pathology are further reviewed. [Gut] Abstract

Circular RNAs in Hepatocellular Carcinoma: Biomarkers, Functions and Mechanisms

Investigators summarize recent findings of deregulated circRNAs, their functions and molecular mechanisms in hepatocellular carcinoma (HCC), and discuss their potential roles as diagnostic biomarkers, prognostic biomarkers, as well as therapeutic targets for HCC. [Life Sci] Abstract | Graphical Abstract

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Arbutus Announces Preliminary Phase Ia/Ib Clinical Trial Results for AB-506, an Oral Capsid Inhibitor in Development for People with Chronic Hepatitis B

Arbutus Biopharma Corporation announced preliminary results from a Phase Ia/Ib clinical trial in healthy subjects and two cohorts of chronic hepatitis B subjects who received AB-506 monotherapy. [Arbutus Biopharma Corporation] Press Release

Dova Pharmaceuticals Announces DOPTELET^® (Avatrombopag) Now Commercially Available in the United States for Treatment of Chronic Immune Thrombocytopenia (ITP)

Dova Pharmaceuticals, Inc. announced the commercial availability of DOPTELET for treatment of thrombocytopenia in adults with chronic ITP who have had an insufficient response to a previous treatment. In June 2019, the FDA approved a supplemental New Drug Application to expand the use of DOPTELET to include this indication. [Dova Pharmaceuticals, Inc.] Press Release

The Plan to Mine the World’s Research Papers

Carl Malamud is on a crusade to liberate information locked up behind paywalls- and his campaigns have scored many victories. Now, the 60-year-old American technologist is turning his sights on a new objective: freeing paywalled scientific literature. And he thinks he has a legal way to do it. [Nature News] Editorial

Virologists Escorted out of Lab in Canada

Canada’s national police force is investigating “possible policy breaches” after researchers were escorted from a lab at Canada’s National Microbiology Laboratory in Winnipeg, CBC News reported. Prominent virologist Xiangguo Qiu, her colleague and husband Keding Cheng, and an unknown number of her students from China were removed from the lab. [The Scientist] Editorial

NEW Tumor Heterogeneity, Plasticity, and Therapy
May 14-15, 2020
Leuven, Belgium

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NEW Postdoctoral Fellow – Hepatitis C Virus (The Research Institute at Nationwide Children’s Hospital)

NEW Postdoctoral Fellow – Inflammatory Liver Disease (The University of Kansas Medical Center)

Project Leader – Chronic Liver Disease Drug Discovery (Inserm Institute for Viral and Liver Disease)

Research Associate – System Level Analysis of Human Organogenesis (The University of Manchester)

Postdoctoral Position – Human Liver Microphysiology Systems (University of Pittsburgh Drug Discover Institute)

Research Professor – Nutrition & Metabolic Diseases (KU Leuven)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Scientist – Epigenetic Mechanisms of NAFLD (Institute of Hepatology, Foundation for Liver Research)

Postdoctoral Position – Liver Disease (University of Illinois at Chicago)

Research Assistant – Liver Immunology (Maynooth University)

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