Hepatic Cell News Volume 3.43 | Nov 15 2019

TOP STORY

Dynamic Regulation of ME1 Phosphorylation and Acetylation Affects Lipid Metabolism and Colorectal Tumorigenesis

PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allowed increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which were reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonized ACAT1 function in a manner that involved mutually exclusive ME1 S336 phosphorylation and K337 acetylation. [Mol Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Large-Scale Production of LGR5-Positive Bipotential Human Liver Stem Cells

Researchers established a new method for the expansion of large quantities of human liver organoids in spinner flasks. Due to improved oxygenation in the spinner flasks, organoids rapidly proliferated and reached an average 40-fold cell expansion after two weeks, compared to six-fold expansion in static cultures. [Hepatology] Abstract

Single-Cell Transcriptomics Uncovers Zonation of Function in the Mesenchyme during Liver Fibrosis

Investigators used single-cell RNA sequencing to deconvolve the hepatic mesenchyme in healthy and fibrotic mouse liver, revealing spatial zonation of hepatic stellate cells (HSCs) across the hepatic lobule. Furthermore, they showed that HSCs partition into topographically diametric lobule regions, designated portal vein-associated HSCs (PaHSCs) and central vein-associated HSCs. [Cell Rep] Full Article | Graphical Abstract

Liver Haploinsufficiency of RuvBL1 Causes Hepatic Insulin Resistance and Enhances Hepatocellular Carcinoma Progression

The authors could determine that RuvBL1 regulates insulin signaling through the Akt/mTOR pathway in liver physiology in vivo as well as in normal hepatocytic and hepatocellular carcinoma cells in vitro. Whole transcriptome analysis of mice livers confirmed the major role of RuvBL1 in the regulation of hepatic glucose metabolism. [Int J Cancer] Abstract | Full Article

LINC01234/MicroRNA-31-5p/MAGEA3 Axis Mediates the Proliferation and Chemoresistance of Hepatocellular Carcinoma Cells

The authors investigated the mechanism how melanoma-associated antigen A3 (MAGEA3) and LINC01234 influenced hepatocellular carcinoma cellular functions and cisplatin resistance. MAGEA3 depletion inhibited proliferation, invasion, and cisplatin resistance of HepG2 cells and Huh7 cells in vitro, reduced resistance-associated protein 2 (MRP2), MRP3, and multidrug resistance protein 1 expression and elevated ALB expression. [Mol Ther Nucleic Acids] Abstract

LncRNA MAGI2-AS3, Regulated by BRD4, Is an Independent Prognostic Marker and Promotes Gastric Cancer Progression via Maintaining ZEB1 Overexpression

MAGI2-AS3 was identified to be an EMT related lncRNA and was highly co-expressed with ZEB1/2 in both gastric cancer (GC) tissues and normal stomach tissues. Loss-of-function and gain-of-function studies showed that lncRNA MAGI2-AS3 could positively regulate ZEB1 expression and the process of cell migration and invasion in GC. Subcellular location assay showed that lncRNA MAGI2-AS3 was mainly located in cytoplasm of GC cells. [Mol Ther Nucleic Acids] Abstract | Full Article

Tanshinone IIA Mediates SMAD7-YAP Interaction to Inhibit Liver Cancer Growth by Inactivating the Transforming Growth Factor Beta Signaling Pathway

The authors found that Tanshinone IIA (Tan IIA) mediated SMAD7-YAP interaction to induce liver cancer cell apoptosis and inhibited cell growth and migration by inactivating the transforming growth factor beta (TGF-β) signaling pathway. Their findings showed that the Tan IIA-SMAD7-YAP regulatory network might be an effective strategy for liver cancer treatment. [Aging (Albany NY)] Full Article

High-Throughput Screening to Evaluate Inhibition of Bile Acid Transporters Using Human Hepatocytes Isolated from Chimeric Mice

Hepatocytes isolated from chimeric mice with humanized livers presented gene expression resembling that of the human liver, and demonstrated apical membrane polarity when sandwiched between Matrigel and collagen. The fluorescent bile acid-derivative cholyl-L-lysyl-fluorescein was used to quantify drug-induced efflux transport inhibition in hepatocytes. [Toxicol Sci] Abstract

LncRNA Meg8 Suppresses Activation of Hepatic Stellate Cells and Epithelial-Mesenchymal Transition of Hepatocytes via the Notch Pathway

Investigators found that Meg8 was over-expressed in activated hepatic stellate cells (HSCs), injured hepatocytes (HCs) and fibrotic livers. They revealed that Meg8 suppressed the expression of the pro-fibrogenic and proliferation genes in activated HSCs. [Biochem Biophys Res Commun] Abstract | Full Article

The Modulatory Effect of Triclosan on the Reversion of the Activated Phenotype of LX-2 Hepatic Stellate Cells

Researchers evaluated cellular and molecular actions of the chemical triclosan in reverting activated hepatic stellate cells (HSCs) to a quiesced phenotype. They demonstrated that the inhibition of the enzyme fatty acid synthase by triclosan in activated HSCs promoted survival of the cells and triggered cellular and molecular changes that promoted cellular phenotypic reversion, offering potentially new therapeutic directions. [J Biochem Mol Toxicol] Abstract

Evaluation of NV556, a Novel Cyclophilin Inhibitor, as a Potential Antifibrotic Compound for Liver Fibrosis

NV556 potential antifibrotic effect was evaluated in two well-established animal models of nonalcoholic steatohepatitis, STAM, and methionine-choline-deficient (MCD) mice, as well as in an in vitro 3D human liver ECM culture of LX2 cells, a human hepatic stellate cell line. They demonstrated that NV556 decreased liver fibrosis in both STAM and MCD in vivo models and decreased collagen production in TGFβ1-activated hepatic stellate cells in vitro. [Cells] Full Article

Subscribe to one of our other 19 science newsletters such as Intestinal Cell News & Pancreatic Cell News.

A Role for the Biological Clock in Liver Cancer

The authors recapitulate the state-of-the-art knowledge on the interplay between the biological clock and the oncogenic pathways and mechanisms involved in hepatocarcinogenesis. They propose how a deeper understanding of circadian clock circuitry-cancer pathways’ crosstalk is promising for developing new strategies for hepatic cell carcinoma prevention and management. [Cancers] Abstract | Download Full Article

TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis

Investigators summarize recent discoveries and milestones on the TGF-β signaling pathway related to liver fibrosis and hepatic stellate cell activation, emphasizing research of the last five years. This comprises impact of TGF-β on liver fibrogenesis related biological processes, such as senescence, metabolism, reactive oxygen species generation, epigenetics, circadian rhythm, epithelial mesenchymal-transition, and endothelial-mesenchymal transition. [Cells] Abstract | Download Full Article

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

Galectin Therapeutics Reaches Agreement with Siemens Healthineers to Collaborate on NASH and Liver Fibrosis

Galectin Therapeutics Inc. announced a collaboration agreement with Siemens Healthineers, a global leader in medical technology, in nonalcoholic steatohepatitis (NASH) and liver fibrosis. This collaboration allows Siemens Healthineers to use Galectin’s Phase II NASH-CX clinical trial to support regulatory filings of the ADVIA Centaur^® Enhanced Liver Fibrosis test. [Galectin Therapeutics] Press Release

OSE Immunotherapeutics Announces Licensing Deal for Neoepitope Combination Tedopi^® in Korea with Chong Kun Dang Pharmaceutical Corporation

OSE Immunotherapeutics announced a new licensing deal with Chong Kun Dang Pharmaceutical Corporation for Tedopi^®, a combination of neoepitopes selected and optimized from five tumor antigens shown to generate a specific response of cytotoxic T cells versus cancer cells expressing at least one of these tumor associated antigens and an associated T-helper cell response, for potential registration and commercialization in Korea. [OSE Immunotherapeutics] Press Release

US Food and Drug Administration Accepts for Priority Review Bristol-Myers Squibb’s Application for Opdivo (Nivolumab) plus Yervoy (Ipilimumab) Combination for Patients with Previously Treated Advanced Hepatocellular Carcinoma

Bristol-Myers Squibb Company announced that the FDA has accepted its supplemental Biologics License Application and granted Breakthrough Therapy Designation for Opdivo in combination with Yervoy for the treatment of patients with advanced hepatocellular carcinoma previously treated with sorafenib. [Bristol-Myers Squibb] Press Release

EPA’s ‘Secret Science’ Plan Is Back, and Critics Say It’s Worse

Critics are blasting a revised Trump administration plan to give the US Environmental Protection Agency (EPA) broad power to ignore research results when setting public health rules if officials decide the underlying data are not adequately accessible to the public. [ScienceInsider] Editorial

The Mental Health of PhD Researchers Demands Urgent Attention

Two years ago, a student responding to Nature’s biennial PhD survey called on universities to provide a quiet room for “crying time” when the pressures caused by graduate study become overwhelming. At that time, 29% of 5,700 respondents listed their mental health as an area of concern – and just under half of those had sought help for anxiety or depression caused by their PhD study. Things seem to be getting worse. [Nature News] Editorial

NEW Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies
January 9-12, 2020
San Diego, California, United States

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

NEW Postdoctoral Researcher – Oncogenic Pathways (University of Liège)

NEW Faculty Member – Pathogen-Associated Malignancies (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Drug-Induced Liver Injury (Johnson & Johnson)

Postdoctoral Researcher – Liver Disease Treatment (University of Southern Denmark)

Postdoctoral Researcher – Personalized Medicine (Mayo Clinic Center for Individualized Medicine)

Postdoctoral Researcher – Liver Plasticity (University of Southern Denmark)

Postdoctoral Scientist – RAS Cancer Biology (Genetech, Inc.)

Assistant Professor – Liver Research (The University of Hong Kong)

Research Scientist – Fibrosis (Gilead Sciences, Inc.)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Hepatic Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.