Hepatic Cell News Volume 3.14 | Apr 26 2019

TOP STORY

Basal Expression of Interferon Regulatory Factor 1 Drives Intrinsic Hepatocyte Resistance to Multiple RNA Viruses

Scientists depleted antiviral factors linked to RIG-I-like receptor and Toll-like receptor signaling to map critical host pathways restricting positive-strand RNA virus replication in immortalized hepatocytes and identified an unexpected role for interferon regulatory factor 1. [Nat Microbiol] Abstract | Press Release

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Promotion of Growth Factor Signaling as a Critical Function of β-Catenin during HCC Progression

The authors revealed that β-catenin nuclear accumulation was restricted to the late stage of the disease. Until then, β-catenin was primarily located at the plasma membrane in complex with multiple cadherin family members where it drives tumor cell survival by enhancing the signaling of growth factor receptors such as epidermal growth factor receptor. [Nat Commun] Full Article

Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma via the miR-338-3p/PKM2 Axis under Hypoxic Stress

Investigators demonstrated that circular RNA MAT2B upregulated expression levels of the miR-338-3p target gene PKM2, which encodes a key enzyme in the process of glycolysis, through ‘sponging’ miR-338-3p; thus, glycolysis and hepatocellular carcinoma progression are promoted via this mechanism. [Hepatology] Abstract

P300 Acetyltransferase Is a Cytoplasm-to-Nucleus Shuttle for SMAD2/3 and TAZ Nuclear Transport in TGFβ-Stimulated Hepatic Stellate Cells

Coimmunoprecipitation, immunofluorescence, and nuclear fractionation assays revealed that TGFβ1 promoted binding of SMAD2/3 and TAZ to p300 and that p300 inactivation disrupted TGFβ1-mediated SMAD2/3 and TAZ nuclear accumulation. Deleting the p300 nuclear localization signal blocked TGFβ1-induced SMAD2/3 and TAZ nuclear transport. [Hepatology] Abstract

NLRP12 Suppresses Hepatocellular Carcinoma via Downregulation of cJun N-Terminal Kinase Activation in the Hepatocyte

Signaling analyses demonstrated higher JNK activation in Nlrp12^-/- hepatocellular carcinoma and cultured hepatocytes during stimulation with microbial pattern molecules. JNK inhibition or NLRP12 overexpression reduced proliferative and inflammatory responses of Nlrp12^-/- hepatocytes. [eLife] Full Article

MicroRNA-196a/-196b Regulate the Progression of Hepatocellular Carcinoma through Modulating the JAK/STAT Pathway via Targeting SOCS2

Knockdown of miR-196a or miR-196b suppressed cell proliferation, glycolysis, cell cycle process, colony formation but induced apoptosis or necrosis in hepatocellular carcinoma (HCC) cells. Suppressor of cytokine signaling 2 (SOCS2) was targeted by miR-196a and miR-196b and its interference ablated abrogation of miR-196a or miR-196b-mediated inhibitory effect on HCC progression. [Cell Death Dis] Full Article

Genome-Wide CRISPR Knockout Screens Identify NCAPG as an Essential Oncogene for Hepatocellular Carcinoma Tumor Growth

Non-structural maintenance of chromosomes condensin I complex subunit G (NCAPG) was ranked the highest among the depletion screens and multiple hepatocellular carcinoma expression datasets. Transient inhibition of NCAPG using specific small interfering RNAs resulted in a significant reduction in cell growth, migration, and the down-regulation of mitochondrial gene expression in vitro. [FASEB J] Abstract

Hepatitis B Virus Precore Protein p22 Inhibits Interferon-Alpha Signaling by Blocking STAT Nuclear Translocation

Scientists report that the cytosolic p22 protein, but not the secreted hepatitis B e antigen, significantly reduced interferon stimulated response element activity and expression of interferon stimulated genes upon alpha interferon stimulation in cell cultures. [J Virol] Abstract

Mistletoe Extract Fraxini Inhibits the Proliferation of Liver Cancer by Down-Regulating c-Myc Expression

Researchers suggest that Fraxini substantially down-regulated c-Myc expression in Hep3B cells. Fraxini-induced growth inhibition was less pronounced in c-Myc knockdown Hep3B cells than in control cells. Furthermore, in the Hep3B xenograft model, Fraxini-treated mice had significantly smaller tumors than control mice. [Sci Rep] Full Article

LINC01018 Confers a Novel Tumor-Suppressor Role in Hepatocellular Carcinoma through Sponging MicroRNA-182-5p

It was observed that LINC01018 and forkhead box protein O1 (FOXO1) were poorly expressed but miR-182-5p was highly expressed in hepatocellular carcinoma (HCC) tissues and cells. The up-regulation of LINC01018 was shown to decrease proliferation while promoting apoptosis of HCC cells. LINC01018 acted as a sponge of miR-182-5p, which targeted FOXO1. [Am J Physiol Gastrointest Liver Physiol] Abstract

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Past, Present and Future Perspectives in Nonalcoholic Fatty Liver Disease

A timeline of scientific discovery of both basic disease mechanisms and the evolution of knowledge about the clinical course of the disease is provided and related to current approaches to treat and eventually prevent nonalcoholic fatty liver disease. [Nat Rev Gastroenterol Hepatol] Abstract

From NASH to HCC: Current Concepts and Future Challenges

The authors discuss nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC), including its epidemiology, the key features of the hepatic NAFLD microenvironment that promote hepatocarcinogenesis and the management of HCC in patients with obesity and associated metabolic comorbidities. [Nat Rev Gastroenterol Hepatol] Abstract

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Promethera Biosciences Presents Updated Phase IIa Results for World’s First Stem Cell Clinical Trial in ACLF

Promethera Biosciences SA announced clinical data from the ongoing Phase IIa study of its lead product candidate HepaStem^® in patients with acute-on-chronic liver failure (ACLF) or acute decompensation at high risk of developing ACLF. [Press release from Promethera Biosciences SA discussing research presented at The International Liver Congress™ (ILC) 2019, Vienna] Press Release

Gilead and Insitro Announce Strategic Collaboration to Discover and Develop Novel Therapies for Nonalcoholic Steatohepatitis

Gilead Sciences Inc. and Insitro announced that the companies have entered into a strategic collaboration to discover and develop therapies for patients with nonalcoholic steatohepatitis (NASH). Under the terms of the three-year collaboration, Insitro’s proprietary platform will be utilized to create disease models for NASH and discover targets that have an influence on clinical progression and regression of the disease. [Gilead Sciences Inc.] Press Release

Tiziana Reports Encouraging Interim Clinical Data from an Ongoing Phase IIa Trial with Milciclib in Advanced Liver Cancer Patients

Tiziana Life Sciences plc announced results from the interim safety review conducted by the Independent Data Monitoring Committee (IDMC). The IDMC reviewed safety data from patients, and concluded that the administration of milciclib to patients with advanced hepatocellular carcinoma was not associated with unexpected signs or signals of toxicity. [Tiziana Life Sciences plc] Press Release

Arrowhead Begins Triple Combination Cohort in Chronic HBV Patients and Earns $25 Million Milestone Payment from Janssen

Arrowhead Pharmaceuticals Inc. announced that it has begun dosing in a new triple combination cohort that includes JNJ-3989 and additional undisclosed agents selected by Janssen Pharmaceuticals, Inc. in its ongoing Phase I/II study in patients with chronic hepatitis B virus (HBV). [Arrowhead Pharmaceuticals Inc.] Press Release

US Universities Reassess Collaborations with Foreign Scientists in Wake of NIH Letters

Kuspa’s attempt to stay ahead of the US National Institutes of Health (NIH) came to naught. A few months into the audit, Baylor College of Medicine received letters from the NIH asking about four scientists it believed had violated the agency’s rule requiring them to disclose all foreign ties relating to their research. [ScienceInsider] Editorial

Elsevier Strikes Its First National Deal with Large Open-Access Element

After a year of talks, Dutch publishing giant Elsevier has struck a deal with a group of Norwegian universities that will allow academics to publish the vast majority of their work under open-access terms. [Nature News] Editorial

NEW Keystone Symposia: Tumor Metabolism
March 8-12, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Fellow – Profiling Single Exosomes & Liver Metastasis Research (McGill University)

NEW Postdoctoral Research Fellow – Organ on a Chip Organoid Development (Universtiy of Oslo)

NEW Research Scientist – Head of the Human Liver Cell Isolation Lab (University of California, San Diego)

NEW Postdoctoral Researcher – Liver Mutagenesis (IRSET)

Postdoctoral Fellow – Fatty Liver Disease Research (Northeast Ohio Medical Universtiy)

Staff Scientist – Liver Disease Research (National Institute of Diabetes and Digestive and Kidney Diseases)

Cell Biologist – Regenerative Medicine & Liver Disease (Hepatx Corporation)

Postdoctoral Research Scholarship – Liver Function & Disease (Karolinska Institutet)

Postdoctoral Research Fellow – Biology of Liver Cancer (Boston Children’s Hospital)

Postdoctoral Position – Stem Cell Biology (University of Zurich)

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