Hepatic Cell News Volume 2.29 | Aug 3 2018

TOP STORY

RAR-β Is Downregulated in HCC & Cirrhosis and Its Expression Inhibits Myosin-Driven Activation and Durotaxis in Hepatic Stellate Cells

Researchers found that retinoic acid receptor beta (RAR-β) expression was significantly reduced in cirrhotic and hepatocellular carcinoma (HCC) tissues. Using a comprehensive set of biophysical methods combined with cellular and molecular biology, they elucidated the biomechanical mechanism by which all trans-retinoic acid promoted hepatic stellate cell deactivation via RAR-β-dependent transcriptional downregulation of myosin light chain 2 expression. [Hepatology] Abstract

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Canonical Wnt Signaling Remodels Lipid Metabolism in Zebrafish Hepatocytes following Ras Oncogenic Insult

Double-transgenic zebrafish larvae conditionally expressing human CTNNB1mt and zebrafish tcf7l2 or murine Myc together with krasv12 in hepatocytes led to severe hepatomegaly and significantly attenuated accumulation of lipid droplets and cell senescence triggered by krasv12 expression alone. [Cancer Res] Abstract

Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies

Investigators reported the generation of long-term organoid cultures from tumor needle biopsies of hepatocellular carcinoma patients with various etiologies and tumor stages. In a proof-of-principle study, they showed that liver cancer organoids could be used to test sensitivity to sorafenib. [Cell Rep] Full Article | Graphical Abstract

Hepatic NF-kB-Inducing Kinase (NIK) Suppresses Mouse Liver Regeneration in Acute and Chronic Liver Disease

Scientists identifed Map3k14 (also known as NIK) and its substrate Chuk as unrecognized suppressors of hepatocyte replication. They found that hepatocyte-specific deletion of Map3k14 or Chuk substantially accelerated mouse hepatocyte proliferation and liver regeneration following partial-hepatectomy. [Elife] Abstract

PTBP3 Splicing Factor Promotes Hepatocellular Carcinoma by Destroying the Splicing Balance of NEAT1 and Pre-miR-612

PTBP3 promoted HCC cell proliferation and metastasis both in vitro and in vivo. RNA immunoprecipitation, fluorescence in situ hybridization and qRT-PCR assays verified that PTBP3 protein recruited abundant lnc-NEAT1 splicing variants and pre-miR-612 in the nucleus. [Oncogene] Abstract

Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells

Researchers utilized three-dimensional, scaffold-free spheroid cultures of human telomerase-immortalized adult liver stem cells HL1-hT1 to evaluate hepatotoxic potential of microcystin-LR and cylindrospermopsin. [Environ Sci Technol] Abstract

circFBLIM1 Act as a ceRNA to Promote Hepatocellular Cancer Progression by Sponging miR-346

Expression levels of a significantly upregulated circular RNA, circFBLIM1, was detected by quantitative real-time PCR in hepatocellular cancer (HCC) cell lines and tissues. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346. [J Exp Clin Cancer Res] Full Article

Fc-Apelin Fusion Protein Attenuates Lipopolysaccharide-Induced Liver Injury in Mice

Co-administration of Fc-apelin significantly attenuated serum ALT elevation, diminished lipopolysaccharide-induced apoptosis and ROS production in the liver and in Huh-7 cells, mitigated hepatic macrophage infiltration, and reduced TNFα and IL-6 gene expression. [Sci Rep] Full Article

17β-Estradiol Inhibits Testosterone-Induced Cell Proliferation in HepG2 by Modulating the Relative Ratios of 3 Estrogen Receptor Isoforms to the Androgen Receptor

Flow cytometry analysis revealed that combined treatment of 17β-estradiol and testosterone blocked the cell cycle in the G0/G1 phase as well as induced cell early apoptosis, characterized by decreased cyclin-dependent kinase transcription and the ratio of Bcl-2/Bax. [J Cell Biochem] Abstract

2,3,7,8-Tetrachlorodibenzo-P-Dioxin Suppresses the Growth of Human Liver Cancer HepG2 Cells In Vitro: Involvement of Cell Signaling Factors

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were dependent on the concentration of serum, which contains various signaling factors. The results of western blot analysis revealed that TCDD increased the protein levels of p53, Rb, p21, and regucalcin, which are suppressors of the growth of tumor cells. [Int J Oncol] Abstract

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Molecular Therapies and Precision Medicine for Hepatocellular Carcinoma

The authors summarize the molecular targets and therapies for the management of hepatocellular carcinoma and discuss the advancements expected in the near future, including biomarker-driven treatments and immunotherapies. [Nat Rev Clin Oncol] Abstract

Statins: Old Drugs As New Therapy for Liver Diseases?

Investigators review the present literature on arrest-defective 1 (ARD1). First, they provide an overview of the essential structure, functions, and molecular mechanisms or pathways of ARD1 in hepatocellular carcinoma. Next, they discuss potential clinical implications and perspectives. [J Hepatol] Full Article

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

Engineering Muscles and Organs in Space

The National Science Foundation has invested in two projects for fundamental biomedical engineering research onboard the International Space Station U.S. National Laboratory for the benefit of life on Earth. [National Science Foundation] Press Release

SomaGenics Awarded Multi-Year Funding for Hepatitis Delta Virus Therapeutic Program

SomaGenics, Inc. announced the award of a three-year, $2.9 million NIH grant in support of its Hepatitis Delta Virus therapeutic program under Principal Investigator and SomaGenics CEO Brian H. Johnston, Ph.D. [SomaGenics, Inc. (PR Newswire Association LLC.)] Press Release

Gigantic Review of German Science Recommends More Data and Diversity

Germany’s largest research organization is funding top-notch science, but it needs to employ more foreign and female researchers — and it is failing to leverage ‘big data’, such as electronic medical records. [Nature News] Editorial

Brexit Preparedness: EMA to Further Temporarily Scale Back and Suspend Activities

The European Medicines Agency (EMA) will launch the next phase of its business continuity plan on 1 October 2018 at the latest. This will allow the Agency to safeguard core activities related to the evaluation and supervision of medicines, while it has to intensify its preparations for the physical move to Amsterdam in March 2019 and cope with significant staff loss. [European Medicines Agency] Press Release

March of Dimes Abruptly Scales Back Research Funding

March of Dimes, the 80-year-old nonprofit organization that has funded pioneering studies on premature birth, infant mortality, and birth defects, is abruptly scaling back its investment in research amid financial struggles—catching scientists by surprise. [ScienceInsider] Editorial

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February 25-26, 2019
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NEW Postdoctoral Fellow Positions – Metabolic Disorders (Temple University School of Medicine)

NEW Research Faculty Position in Diabetes, Obesity, and Metabolism (University of Pittsburgh)

PhD Positions – Non-Alcoholic Fatty Liver Disease (The Leibniz Institute for Natural Product Research and Infection Biology)

Postdoctoral Position – High-Throughput Functional Screening of iPSC-Derived Models (KU Leuven)

Postdoctoral Fellow – Computational Approaches to Prioritize Drugs and Drug Targets for Cancer Therapeutics (European Molecular Biology Laboratory)

Postdoctoral Position – Liver Cancer Translational Research (IDIBAPS)

Postdoctoral Fellows – Translational Oncology (Baylor College of Medicine)

Postdoctoral Fellow – Liver Cancer (Loyola University Chicago)

Postdoctoral Position – Necroptosis in Liver Diseases (Inserm)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

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