Hepatic Cell News Volume 3.16 | May 10 2019

TOP STORY

Researchers at IRB Barcelona Identify a Protein that Protects against Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease describes several liver dysfunctions of varying severity, characterized by the accumulation of fat in hepatic cells and not caused by high alcohol consumption. A team at the Institute for Research in Biomedicine (IRB Barcelona) has identified one of the factors that confer protection against this condition, namely the protein Mitofusin 2. [Press release from the Institute for Research in Biomedicine discussing online prepublication in Cell] Press Release | Abstract

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Single-Cell Analysis of the Liver Epithelium Reveals Dynamic Heterogeneity and an Essential Role for YAP in Homeostasis and Regeneration

Scientists performed single-cell RNA sequencing to examine biliary epithelial cells (BECs) and hepatocyte heterogeneity during homeostasis and after injury. Instead of evidence for a transcriptionally defined progenitor-like BEC cell, they found significant homeostatic BEC heterogeneity that reflected fluctuating activation of a YAP-dependent program. [Cell Stem Cell] Abstract | Graphical Abstract

Analysis of Liver Cancer Cell Lines Identifies Agents with Likely Efficacy against Hepatocellular Carcinoma and Markers of Response

Investigators performed whole-exome RNA and microRNA sequencing and quantification of 126 proteins in 34 liver cancer cell lines (LCCLs). They screened 31 anti-cancer agents for their ability to decrease cell viability. They compared genetic, RNA, and protein profiles of LCCLs with those of primary hepatocellular carcinoma samples and searched for markers of response. [Gastroenterology] Abstract

Complement C3 Activation Regulates the Production of tRNA-Derived Fragments Gly-tRFs and Promotes Alcohol-Induced Liver Injury and Steatosis

Mechanistically, glycine transfer (t) RNA-derived fragments (Gly-tRFs) interacted with AGO3 to downregulate sirtuin1 (Sirt1) expression via sequence complementarity in the 3′ UTR. Notably, the expression levels of C3d, CYP2E1 and Gly-tRF were upregulated, whereas Sirt1 was decreased in alcoholic fatty liver disease patients compared to healthy controls. [Cell Res] Full Article

Dyrk3 Loss Activates the Purine Metabolism and Promotes Hepatocellular Carcinoma Progression

The authors explored the role of Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3 (Dyrk3) in hepatocellular carcinoma (HCC) metabolism. Dyrk3 was significantly downregulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppressed tumor growth and metastasis in xenograft tumor models. [Hepatology] Abstract

The mTORC2-Akt Cascade Is Crucial for c-Myc to Promote Hepatocarcinogenesis in Mice and Men

Scientists discovered that loss of Akt1, but not Akt2, completely prevented c-Myc hepatocellular carcinoma (HCC) formation in mice. Silencing of Rictor or Akt1 in c-Myc HCC cell lines inhibited p-Foxo1 expression and strongly suppressed cell growth in vitro. [Hepatology] Abstract

Dual Delivery of HNF4α and Cisplatin by Mesoporous Silica Nanoparticles Inhibits Cancer Pluripotency and Tumorigenicity in Hepatoma-Derived CD133-Expressing Stem Cells

Researchers investigated an approach to target hepatocellular carcinoma by combining conventional chemotherapeutic drug cisplatin to target the bulk of tumor cells, and differentiation therapy by delivering the gene encoding HNF4α, an important regulator of hepatocyte differentiation, to target cancer stem cells. [ACS Appl Mater Interfaces] Abstract

Lipopolysaccharide Induces the Differentiation of Hepatic Progenitor Cells into Myofibroblasts Constitutes the Hepatocarcinogenesis-Associated Microenvironment

Investigators showed that lipopolysaccharides/Toll-like receptor 4 signaling mediated the differentiation of hepatic progenitor cells (HPCs) into myofibroblasts and enhanced the production of interleukin-6 and tumor necrosis factor-α, which led to the aberrant expression of Ras and p53 signaling pathways in HPCs, and finally, promoted the proliferation and malignant transformation of HPCs, by long non-coding RNA regulation. [Cell Death Differ] Abstract

Liver Stage Malaria Infection Is Controlled by Host Regulators of Lipid Peroxidation

The authors showed previously that increased levels of P53 reduces Plasmodium liver stage burden in an apoptosis-independent manner. Here, they demonstrated that increased P53 was unable to control parasite burden during NOX1 or TFR1 knockdown, or in the presence of reactive oxygen species scavenging or when lipid peroxidation was blocked. Additionally, SLC7a11 inhibitors erastin and sorafenib reduced infection. [Cell Death Differ] Full Article

LncRNA SNHG1 Contributes to Sorafenib Resistance by Activating the Akt Pathway and Is Positively Regulated by miR-21 in Hepatocellular Carcinoma Cells

Overexpressed small nucleolar RNA host gene 1 (SNHG1) contributed to sorafenib resistance by activating the Akt pathway via regulating SLC3A2. Depletion of SNHG1 enhanced the efficacy of sorafenib to induce apoptosis and autophagy of sorafenib-resistatnt hepatocellular carcinoma cells by inhibiting the activation of the Akt pathway. [J Exp Clin Cancer Res] Full Article

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Homeobox Genes and Hepatocellular Carcinoma

The authors summarize the currently available evidence related to the role of homeobox genes in the development of hepatocellular carcinoma. They determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations. [Cancers] Full Article

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Can-Fite Announces Preparation for End-of-Phase II Meeting with FDA to Initiate the Phase III Liver Cancer Study for Namodenoson

Can-Fite BioPharma Ltd. announced it is conducting preparatory work for a planned pivotal Phase III study of its drug candidate Namodenoson in the treatment of advanced liver cancer in patients as a first line and second line treatment. [Can-Fite BioPharma Ltd.] Press Release

DURECT Corporation Announces Preliminary Data from the Ongoing DUR-928 Alcoholic Hepatitis Phase IIa Trial

DURECT Corporation announced preliminary data from the ongoing DUR-928 alcoholic hepatitis Phase IIa clinical trial. Ten patients have completed dosing with DUR-928 to date in the ongoing open label, dose-escalation, multi-center US trial. Eight patients have been treated with DUR-98 at the 30 mg dose, and two patients at the 90 mg dose. [DURECT Corporation] Press Release

Promethera Biosciences Announces First-Dosing in Phase IIa Clinical Study Evaluating World’s First Liver Stem Cell Therapy in Late-Stage NASH Patients

Promethera Biosciences SA announced the dosing of a first patient in a Phase IIa clinical study for the company’s HepaStem development program in patients with late stage non-alcoholic steatohepatitis (NASH). The multicenter, open-label PANASH study will evaluate the safety and preliminary efficacy of Promethera’s investigational drug HepaStem, a novel allogenic cell-based therapy for severe liver diseases, in patients with cirrhotic and pre-cirrhotic NASH. [Promethera Biosciences SA] Press Release

Enzo Biochem Inc. Announces Issuance of United States Patent for Treatment of Liver Cancer Using Ozanimod

Enzo Biochem, Inc. announced that it was issued US Patent No. 10,278,960 entitled “Sphingosine Pathway Modulating Compounds for the Treatment of Cancers” that is directed to methods for treating hepatocellular carcinoma, the most common human liver cancer, using the compound Ozanimod. [Enzo Biochem, Inc.] Press Release

Dr. Tamara Zietek discusses the use of intestinal organoids as a model system for nutrient transport. Listen Now

Intolerance and Funding Concern Indian Scientists ahead of Election

A rising intolerance towards intellectuals and minority groups in India has prompted scientists there to speak out ahead of the country’s mammoth general election. More than 200 scientists have signed an open letter appealing to citizens to reject the discrimination and violence being promoted by some extremist groups. [Nature News] Editorial

Brazilian Biomedical Science Faces Reproducibility Test

An ambitious project to test the reproducibility of biomedical experiments by Brazilian scientists is about to get under way. The Brazilian Reproducibility Initiative was launched last year by researchers at the Federal University of Rio de Janeiro. Now, the first wave of reproducibility testing is set to begin in August, with help from more than 60 laboratories scattered over 43 Brazilian research centers. [Nature News] Editorial

US Lawmakers Propose Plan to Reduce Primate Research at National Institutes of Health

The US National Institutes of Health (NIH) would be required to reduce its use of non-human primates in research, under a spending bill approved on 8 May by a committee in the US House of Representatives. The bill would direct the NIH “to accelerate efforts to reduce and replace the use of nonhuman primates with alternative research models” in its laboratories. [Nature News] Editorial

NEW 8^th InterAmerican Oncology Conference
October 17-18, 2019
Buenos Aires, Argentina

Visit our events page to see a complete list of events in the community.

NEW Research Assistant – Liver Damage Research (University of Colorado Denver)

Tier I CIHR Canada Research Chair – Mechanisms of Health & Disease (Brock University)

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

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

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

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)

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

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

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