Hepatic Cell News Volume 4.15 | May 1 2020

TOP STORY

PLAGL2-EGFR-HIF-1/2α Signaling Loop Promotes HCC Progression and Erlotinib Insensitivity

The authors demonstrated that pleomorphic adenoma gene like-2 (PLAGL2) was upregulated in hepatocellular carcinoma (HCC) compared to that of adjacent non-tumorous tissues. PLAGL2 promoted HCC cell proliferation, migration, and invasion both in vitro and in vivo. [Hepatology] Abstract

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Functional Comparison of IFN-α Subtypes Reveals Potent HBV Suppression by a Concerted Action of IFN-α and -γ Signaling

Scientists deepened the understanding of the mechanism underlying the synergism between IFN-α and -γ signaling. They identified GBP5, one of the most differentially-expressed genes between IFN-α14- and -α2-treated liver cells, as a new hepatitis B virus restriction factor. [Hepatology] Abstract

LGR5 Marks Targetable Tumor-Initiating Cells in Mouse Liver Cancer

Researchers reported the enrichment of LGR5 expressing cells, a well-recognized stem cell marker, in mouse liver tumors, and the upregulation of LGR5 expression in human hepatocellular carcinoma. [Nat Commun] Full Article

Mechanistic Differences in Cell Death Responses to Metal-Based Engineered Nanomaterials in Kupffer Cells and Hepatocytes

Investigators conducted a toxicological profiling of metal-based nanoparticles in Kupffer cell and hepatocyte cell lines and improved understanding of the mechanisms of metal-based engineered nanomaterial toxicity in liver cells. [Small] Abstract

Quantitative Analysis of Amino Acid Metabolism in Liver Cancer Links Glutamate Excretion to Nucleotide Synthesis

Scientists dynamically profiled the uptake and excretion fluxes of glutamine in a hepg2 liver cancer cell line and used genome-scale metabolic modeling for in-depth analysis. They found that up to 30% of glutamine was metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. [Proc Natl Acad Sci USA] Full Article

SAMD4 Family Members Suppress Human Hepatitis B Virus by Directly Binding to the Smaug Recognition Region of Viral RNA

SAMD4A, a human interferon-stimulated gene (ISG), was an important anti-hepatitis B virus (HBV) ISG for use in IFN therapy of hepatitis B. Researchers suggested that the levels of SAMD4A/B expression were related to HBV sensitivity in humans. [Cell Mol Immunol] Abstract

miR-486-3p Mediates Hepatocellular Carcinoma Sorafenib Resistance by Targeting FGFR4 and EGFR

The authors aimed to investigate the mechanisms of sorafenib resistance and provided possible targets for combination therapies. Through miRNA sequencing, they found that miR-486-3p was downregulated in sorafenib resistant hepatocellular carcinoma cell lines. [Cell Death Dis] Full Article

Sepiapterin Reductase Promotes Hepatocellular Carcinoma Progression via FoxO3a/Bim Signaling in a Nonenzymatic Manner

Investigators found that sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. [Cell Death Dis] Full Article

Disruption of Plin5 Degradation by CMA Causes Lipid Homeostasis Imbalance in NAFLD

HepG2 cells lacking LAMP2A were used to investigate the influence of chaperone-mediated autophagy (CMA) on lipolysis in hepatocytes. They found disrupted CMA function in the livers of nonalcoholic fatty liver disease patients and animal models, displaying obvious reduction of LAMP2A and concurrent with decreased levels of CMA positive regulators. [Liver Int] Abstract

Role of GPRC6A in Regulating Hepatic Energy Metabolism in Mice

Scientists suggested that metabolism regulating G-protein coupled receptor, GPRC6A, directly regulated hepatic metabolism as well as regulated the production and release of FGF-21 to control systemic energy homeostasis. [Sci Rep] Full Article

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Role of Pyroptosis in Liver Diseases

Researchers focused on the role of pyroptosis based on the molecular and pathophysiological mechanisms in the development of liver diseases. They also highlighted targeting of pyroptosis for the therapeutic implications in liver diseases in the near future. [Int Immunopharmacol] Abstract

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FDA Approves Incyte’s Pemazyre™ (pemigatinib) as First Targeted Treatment for Adults with Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma

Incyte have announced that the FDA has approved Pemazyre™, a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 fusion. [Incyte Corporation] Press Release

Galectin Therapeutics Submits Seamless Adaptively-Designed Phase IIb/III NASH-RX Protocol in NASH Cirrhosis

Galectin Therapeutics, Inc. have announced that it has submitted to the FDA its protocol for a seamless adaptively-designed Phase IIb/III clinical study, the NASH-RX trial, evaluating the safety and efficacy of its galectin-3 inhibitor, belapectin, for the prevention of esophageal varices in patients with non-alcoholic steatohepatitis cirrhosis. [Galectin Therapeutics Inc.] Press Release

The Pandemic’s Effects on Recruiting International STEM Trainees

Pandemic-related concerns that have arisen for science trainees-shuttered labs, research and education delays, anxiety-are applicable across the board. But international graduate students and postdocs face a suite of unique challenges that raise uncertainty about recruiting and supporting this critical group of researchers in the future. [The Scientist] Editorial

As COVID-19 Forces Conferences Online, Scientists Discover Upsides of Virtual Format

As the novel coronavirus outbreak shutters businesses and disrupts everyday life for billions around the globe, massive annual conferences and small society meetings alike have moved online. The new format poses numerous technical and organizational challenges, but it also offers opportunities- for reaching wider audiences, reducing the carbon footprint of meeting travel, and improving diversity and equity. [ScienceInsider] Editorial

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NEW Staff Fellow – Viral Vaccines (FDA-Center for Biologics Evaluation and Research)

Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

Postdoctoral Fellow – Molecular Diagnostics and Experimental Therapeutics (City of Hope)

Professorship of Hepatology (Ludwig-Maximilians-Universität)

Senior Research Scientist – Liver Disease (Novo Nordisk)

Scientist – Molecular & Cellular Biology (Deep Genomics, Inc.)

Postdoctoral Position – Gut-Liver Axis (University of California, Davis)

Postdoctoral Position – Liver Pathogenesis (Washington University in St.Louis)

Therapuetic Specialist – Inflammation (Gilead Sciences Inc.)

Team Leader – Cholangiocytes (Miromatrix Medical)

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