Hepatic Cell News Volume 3.37 | Oct 4 2019

TOP STORY

Inducing and Exploiting Vulnerabilities for the Treatment of Liver Cancer

Using a kinome-focused genetic screen, researchers showed that pharmacological inhibition of the DNA-replication kinase CDC7 induced senescence selectively in liver cancer cells with mutations in TP53. A follow-up chemical screen identified the antidepressant sertraline as an agent that killed hepatocellular carcinoma cells that had been rendered senescent by inhibition of CDC7. [Nature] Abstract

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Liver-Derived Signals Sequentially Reprogram Myeloid Enhancers to Initiate and Maintain Kupffer Cell Identity

The authors characterized transcriptomic and epigenetic changes in repopulating liver macrophages following acute Kupffer cell depletion as a means to infer signaling pathways and transcription factors that promoted Kupffer cell differentiation. They obtained evidence that combinatorial interactions of the Notch ligand DLL4 and transforming growth factor-b family ligands produced by sinusoidal endothelial cells and endogenous LXR ligands were required for the induction and maintenance of Kupffer cell identity. [Immunity] Abstract | Graphical Abstract

Intravenous Injections of a Rationally Selected Oncolytic Herpes Virus as a Potent Virotherapy for Hepatocellular Carcinoma

Scientists report the rational generation of a novel HSV-1-based oncolytic vector for targeting hepatocellular carcinoma (HCC), named Ld0-GFP, which was derived from oncolytic ICP0-null virus, had fusogenic phenotype and was a novel killer against HCC as well as other types of cancer cells. Compared with d0-GFP, Ld0-GFP exhibited superior cancer cell killing ability in vitro and in vivo. [Mol Ther] Abstract | Full Article

TXNDC12 Promotes EMT and Metastasis of Hepatocellular Carcinoma Cells via Activation of β-Catenin

Investigators found that the enforced expression of TXNDC12 promoted metastasis both in vitro and in vivo. Subsequent mechanistic investigations revealed that TXNDC12 promoted metastasis through upregulation of the ZEB1-mediated epithelial-mesenchymal transition (EMT) process. [Cell Death Differ] Full Article

NUDT21 Regulates circRNA Cyclization and ceRNA Crosstalk in Hepatocellular Carcinoma

The authors explored the relationship between circular RNA biogenesis and NUDT21, which was a RNA splice factor downregulated in hepatocellular carcinoma, and they found that NUDT21 elevated the formation of circRNA, and the UGUA sequences were critical for the cyclization of circRNA. [Oncogene] Abstract

MicroRNA-17 Functions as an Oncogene by Downregulating Smad3 Expression in Hepatocellular Carcinoma

Using a loss-of-function assay, scientists demonstrated that miR-17 directly targeted Smad3 in hepatocellular carcinoma (HCC) cells and inhibition on miR-17 increased Smad3 expression. Furthermore, they found that downregulation on Smad3 expression was consistent with high level of miR-17 in HCC tissues of patients when compared with around normal liver tissues. [Cell Death Dis] Full Article

LINC00978 Promotes the Progression of Hepatocellular Carcinoma by Regulating EZH2-Mediated Silencing of p21 and E-Cadherin Expression

Mechanistically, LINC00978 bound to EZH2 and mediated its accumulation at the promoter region of p21 and E-cadherin genes, leading to the trimethylation of H27K3 and the inhibition of p21 and E-cadherin expression. Moreover, the simultaneous depletion of p21 and E-cadherin expression reversed the inhibitory effects of LINC00978 knockdown on HCC cell proliferation, migration, and invasion. [Cell Death Dis] Full Article

Human Amniotic Membrane Conditioned Medium Inhibits Proliferation and Modulates Related MicroRNAs Expression in Hepatocarcinoma Cells

Researchers determined by ³H-thymidine incorporation assay that amniotic membrane conditioned medium (AM-CM) inhibited DNA synthesis in HepG2 cells after 72 hours of treatment. AM-CM pure or diluted at 50% and 25% also diminished HepG2 and HuH-7 cells viability and cell number. [Sci Rep] Full Article

Nano-Fibre Integrated Microcapsules: A Nano-in-Micro Platform for 3D Cell Culture

Human liver carcinoma cells, HepG2, were encapsulated into the microcapsules and their physio-chemical properties were studied. Morphology, stability, and chemical composition of the PNA microcapsules were analyzed by light microscopy, fluorescent microscopy, scanning electron microscopy, Fourier-Transform Infrared spectroscopy, and thermogravimetric analysis. [Sci Rep] Full Article

Hypoxia-Induced Exosomes Promote Hepatocellular Carcinoma Proliferation and Metastasis via miR-1273f Transfer

Investigators found that hypoxic conditions induced increased exosomal production by hepatocellular carcinoma (HCC) cells, and these exosomes, in turn, enhanced the proliferation, migration, and invasiveness in addition to epithelial-to-mesenchymal transition in HCC cells under normoxic conditions. [Exp Cell Res] Full Article

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Purinergic Signaling in Hepatic Disease

The authors focus on the role of the purinergic system in liver damage, mainly during the onset and development of fibrosis. After hepatocellular injury, extracellular ATP promotes a signaling cascade that ameliorates tissue alterations to restore the hepatic function. [Purinergic Signal] Abstract

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CytoDyn Announces FDA Clearance to Proceed with Phase II Clinical Trial of Leronlimab (PRO 140) for Treatment of NASH

CytoDyn Inc. announced FDA clearance to initiate enrollment in the company’s Phase II clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). The Phase II trial is designed to test whether leronlimab may control the devastating liver fibrosis associated with NASH. [CytoDyn Inc.] Press Release

Akero Therapeutics and InSphero Partner to Evaluate AKR-001 Using InSphero’s 3D InSight™ Human Liver Disease Platform

Akero Therapeutics and InSphero AG announced that Akero has selected InSphero’s 3D InSight™ Human Liver Disease Platform to characterize the physiological effects of AKR-001 in different types of liver cells. AKR-001 is designed to be a novel, long-acting FGF21 analog, currently being evaluated in a Phase IIa clinical trial for the treatment of non-alcoholic steatohepatitis. [Akero Therapeutics] Press Release

VEO Oncology Announces Initiation of Enrollment in Phase Ib/II Study of FOTIVDA^® (Tivozanib) in Combination with IMFINZI^® (Durvalumab) in Previously Untreated Metastatic Hepatocellular Carcinoma

AVEO Oncology announced that it has initiated enrollment in an open-label, multi-center Phase Ib/II clinical trial evaluating FOTIVDA^®, the company’s once-daily, potent and selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with IMFINZI^®, AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1, in patients with hepatocellular carcinoma who have not received prior systemic therapy. [AVEO Oncology (Business Wire, Inc.)] Press Release

‘More Women Are Being Nominated’: Nobel Academy Head Discusses Diversity

The Royal Swedish Academy of Sciences introduced measures that it hoped would tackle the issue by encouraging scientists to put forward a more diverse range of nominees. These included asking more women to suggest candidates, and altering the wording of the letter inviting nominations. [Nature News] Editorial

Split Decisions: How Brexit Has Taken a Toll on Five Researchers

On 23 June 2016, 34 million UK citizens took to the polls to vote on a simple, fateful question: Should the United Kingdom remain a part of the European Union, or should it leave? Nearly 52%—a majority of 1.3 million—wanted out, and conservative politicians vowed to carry out the people’s wishes. [ScienceInsider] Editorial

Trump Set to Nominate Stephen Hahn as FDA Commissioner, Pending Vetting Process

President Trump is set to nominate Dr. Stephen Hahn to lead the FDA, pending completion of the vetting process, according to two people familiar with the selection process. Hahn, an oncologist, is the chief medical executive at MD Anderson Cancer Center in Houston. [STAT News] Editorial

Human Reference Genome Doesn’t Capture Full Genetic Diversity

It’s hard to study genetic sequences if they’re absent from the human reference genome, the product of the $2.7 billion Human Genome Project, which is typically used as a guide for genomic studies. A new study has identified more than 61,000 novel genetic sequences across 1,000 Swedish genomes that are absent from the human reference genome. [The Scientist] Editorial

NEW Gene Regulation: From Mechanisms to Disease
January 26-30, 2020
Keystone, Colorado, United States

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NEW Postdoctoral Researcher – Gene Regulation in Liver Cancer (Umeå University)

NEW Chief Editor – Nature Ageing (Nature Research)

Research Scientist – Fibrosis (Gilead Sciences, Inc.)

Postdoctoral Researchers – Liver Diseases (Albert Einstein College of Medicine)

Postdoctoral Researcher – Liver Cell-Cell Interactions (Flanders Institute for Biotechnology)

Postdoctoral Researcher – Liver Disease (Albert Einstein College of Medicine)

Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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

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