Hepatic Cell News Volume 2.08 | Mar 2 2018

TOP STORY

SIRT5 Inhibits Peroxisomal ACOX1 to Prevent Oxidative Damage and Is Downregulated in Liver Cancer

Researchers showed that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that acyl‐CoA oxidase 1 (ACOX1) is a physiological substrate of SIRT5. Mechanistically, SIRT5‐mediated desuccinylation inhibited ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. [EMBO Rep] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

USP27-Mediated Cyclin E Stabilization Drives Cell Cycle Progression and Hepatocellular Tumorigenesis

Scientists identified ubiquitin-specific peptidase 27 (USP27) as a Cyclin E interactor. They found that USP27 promoted Cyclin E stability by negatively regulating its ubiquitination. In addition, suppression of USP27 expression resulted in the inhibition of the growth, migration, and invasion of hepatocellular carcinoma. [Oncogene] Full Article

AGO1 May Influence the Prognosis of Hepatocellular Carcinoma through TGF-β Pathway

Using small interfering RNA, AGO1 functions were investigated in HCCLM3 cell lines. Cell proliferation, immigration, and invasion significantly decreased after AGO1 depletion using MTT, wound-healing, and transwell assay. [Cell Death Dis] Full Article

Lack of Hepatic Stimulator Substance Expression Promotes Hepatocellular Carcinoma Metastasis Partly through ERK-Activated Epithelial–Mesenchymal Transition

Scientists demonstrated that downregulation of hepatic stimulator substance expression contributes to hepatocellular carcinoma metastasis partially through the extracellular signal-regulated kinase-activated epithelial–mesenchymal transition pathway. [Lab Invest] Abstract

Functional Innate Immunity Restricts Hepatitis C Virus Infection in Induced Pluripotent Stem Cell–Derived Hepatocytes

Investigators analyzed the suitability of induced pluripotent stem cell-derived hepatocyte-like cells as a physiologically relevant model to study hepatitis C virus replication in vitro. [Sci Rep] Full Article

Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats

To avoid the preparation of stem cells, researchers proposed to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (Archive), an antagonist of CXCR4 and low-dose FK506 (F). They showed that AF combination therapy significantly increased lineage negative (Lin-) CD34+ and Lin-CD133⁺ stem cells in peripheral blood and enhanced recruitment of CD133⁺ cells into the remnant liver in a rat model of 85% partial hepatectomy. [Sci Rep] Full Article

Pharmacological or Transcriptional Inhibition of Both HDAC1 and 2 Leads to Cell Cycle Blockage and Apoptosis via p21^Waf1/Cip1 and p19^INK4d Upregulation in Hepatocellular Carcinoma

The authors investigated the therapeutic effect of selectively inhibiting histone deacetylase 1 (HDAC1) and 2 in hepatocellular carcinoma (HCC). Combined inhibition of HDAC1/2 led to HCC cell morphology changes, growth inhibition, cell cycle blockage and apoptosis in vitro and suppressed the growth of subcutaneous HCC xenograft tumors in vivo. [Cell Prolif] Abstract

NEDD4 Promotes Cell Growth and Motility in Hepatocellular Carcinoma

Researchers found that depletion of neuronally expressed developmentally downregulated 4 (NEDD4) by siRNA transfection led to inhibition of cell growth, invasion and migration, and promotion of apoptosis. In contrast, overexpression of NEDD4 via plasmid transfection resulted in facilitated cell proliferation, invasion and migration, and decreased apoptosis. [Cell Cycle] Abstract

Geranylgeranylacetone Attenuates Fibrogenic Activity and Induces Apoptosis in Cultured Human Hepatic Stellate Cells and Reduces Liver Fibrosis in Carbon Tetrachloride-Treated Mice

Scientists investigated the effects of geranylgeranylacetone on human hepatic stellate cells in vitro and in a mouse model of liver fibrosis. [BMC Gastroenterol] Full Article

Role of Nonresolving Inflammation in Hepatocellular Carcinoma Development and Progression

Accumulating datas from human and mouse models showed that inflammation promotes HCC development by promoting proliferative and survival signaling, inducing angiogenesis, evading immune surveillance, supporting cancer stem cells, activating invasion and metastasis as well as inducing genomic instability. [npj Precis Oncol] Full Article

Visit our reviews page to see a complete list of reviews in the hepatic cell research field.

Poxel Presents Preclinical Proof-of-Concept Data for PXL770 in Non-Alcoholic Steatohepatitis (NASH)

Poxel SA announced the poster presentation of proof-of-concept data for PXL770 in a biopsy-confirmed model of diet-induced NASH. [Press release from Poxel SA discussing research presented at the Global NASH Congress 2018, London] Press Release

New Preclinical Data on MIV-818 Accepted for Presentation

Medivir AB informs that new preclinical data for MIV-818 will be presented. MIV-818 is Medivir’s proprietary nucleotide prodrug that is being developed for the treatment of hepatocellular carcinoma and other liver cancers. [Press release from Medivir AB discussing research to be presented at the EASL Hepatocellular Carcinoma (HCC) Summit, Geneva] Press Release

MD Anderson Receives $22 Million in CPRIT Funding for Research, Prevention and Recruitment

The University of Texas MD Anderson Cancer Center was awarded $22.3 million from the Cancer Prevention and Research Institute of Texas (CPRIT), accounting for 30 percent of the $73.5 million in awards CPRIT announced. The awards included $16.3 million for individual investigator research including awards for cancer in children and adolescents, computational biology, clinical translation, and prevention and early detection. [University of Texas MD Anderson Cancer Center (Newswise, Inc.)] Press Release

DURECT Announces Patient Dosing in Phase IIa Trial of DUR-928 in Primary Sclerosing Cholangitis (PSC)

DURECT Corporation announced it has commenced patient dosing in a Phase IIa clinical trial of DUR-928 in patients with primary sclerosing cholangitis. [DURECT Corporation] Press Release

Can Fite Reports on the Progress of its Phase II NASH Study with Drug Candidate Namodenoson

Can-Fite BioPharma Ltd. provided an update on its Phase II clinical trial with drug candidate Namodenoson in the treatment of NAFLD/NASH. [Can-Fite BioPharma Ltd.] Press Release

EU Research Chief’s Next Act: Changing the Future of Academic Publishing

Robert-Jan Smits, one of Europe’s most powerful figures in research, has been appointed as a special envoy on open science at the European Commission, to help push efforts to make all publicly funded research in Europe freely available by 2020. [Science|Business] Editorial

Here’s How the Scientists Running for Office Are Doing

They’re trained problem-solvers, but they have to learn to move beyond data to run successful campaigns. [The Atlantic] Editorial

Canadian Science Wins Billions in New Budget

Canadian Prime Minister Justin Trudeau’s administration released its 2018 budget and scientists couldn’t be happier. It includes almost CAD 4 billion (USD 3.1 billion) in new funding for science over the next five years, a significant portion of which will go to the country’s three granting councils. [Nature News] Editorial

Indian Scientist’s Sacking Spotlights Sexual Harassment

Female scientists in India hope that more academics will report sexual harassment without fear of jeopardizing their career or reputation, after a prominent biologist was sacked for allegedly harassing a staff member. [Nature News] Editorial

NEW EMBO-EMBL Symposia: Organoids: Modeling Organ Development and Disease in 3D Culture
September 10-13, 2018
Heidelberg, Germany

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

NEW Postdoctoral Research Associate – Liver Diseases (University of Illinois at Chicago)

NEW Postdoctoral Scientist – Acute-on-Chronic Liver Failure (Foundation for Liver Research)

Postdoctoral Research Scientist – Cancer Research (Cancer Research UK Beatson Institute)

Global Clinical Lead – Oncology (AstraZeneca)

Postdoctoral Research Scientist – Hepatocellular Carcinoma (Cancer Research UK Beatson Institute)

Postdoctoral Fellowship – Immunology of Chronic Infections (F. Hoffmann-La Roche AG)

Postdoctoral Fellowship – Translational Cancer Research (Lund University)

Lectureship – Stem Cell Biology and Regenerative Medicine (University of Edinburgh)

Postdoctoral Fellow – Liver Cancer Research (University of California, San Francisco)

Postdoctoral Position – Liver Diseases (University of Illinois)

Postdoctoral Fellow – Liver Cancer (University Health Network)

Postdoctoral Fellow – Liver Tissue Engineering (Massachusetts General Hospital and Harvard Medical School)

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