Hepatic Cell News Volume 1.31 | Sep 1 2017

TOP STORY

Hepatitis B Virus X Protein Promotes the Development of Liver Fibrosis and Hepatoma through Downregulation of miR-30e Targeting P4HA2 mRNA.

Scientists report that hepatitis B virus leads to liver fibrosis and hepatocarcinogenesis through miR-30e targeting prolyl 4-hydroxylase subunit α2 (P4HA2). Hepatitis B virus X protein (HBx) was capable of inducing P4HA2 through suppressing miR-30e, in which miR-30e could target P4HA2 mRNA 3′ untranslated region in liver cancer cells. [Oncogene] Abstract

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Gab2 Mediates Hepatocellular Carcinogenesis by Integrating Multiple Signaling Pathways

Previous studies have found that growth factor receptor-bound protein 2-associated binding protein 2 (Gab2)-a docking protein-governs the development of fatty liver disease. Investigators demonstrated that Gab2 mediates hepatocarcinogenesis. Compared with a faint expression in para-carcinoma tissue, Gab2 was highly expressed in 60-70% of human hepatocellular carcinoma specimens. [FASEB J] Full Article

Olfactory Receptor 10J5 Responding to α-Cedrene Regulates Hepatic Steatosis via the cAMP–PKA Pathway

Using MOR23- and OR10J5-expressing Hana3A cells, researchers identified α-cedrene, a natural compound that protects against hepatic steatosis in mice fed the high-fat diet, as a novel agonist of these receptors. α-Cedrene stimulation resulted in a significant reduction in lipid contents of human hepatocytes and reprogramming of metabolic signatures, which are mediated by OR10J5, as demonstrated by receptor knockdown experiments using RNA interference. [Sci Rep] Full Article

A Novel Three-Dimensional Culture System Maintaining the Physiological Extracellular Matrix of Fibrotic Model Livers Accelerates Progression of Hepatocellular Carcinoma Cells

Scientists created a new culture system that retained the natural extracellular matrix (ECM) of fibrotic model livers and to establish whether natural ECM regulated the characteristics of hepatocellular carcinoma cells. [Sci Rep] Full Article

Epidermal Growth Factor and Tumor Necrosis Factor α Cooperatively Promote the Motility of Hepatocellular Carcinoma Cell Lines via Synergistic Induction of Fibronectin by NF-κB/p65

The authors demonstrated that both epidermal growth factor (EGF) and tumor necrosis factor α (TNFα) were highly expressed in hepatocellular carcinomas (HCCs), and HCCs with higher expression of both EGF and TNFα were more frequently rated as high-grade tumors. In vitro, EGF and TNFα cooperatively promoted the motility of HCC cells mainly via synergistic induction of an extracellular matrix glycoprotein fibronectin. [Biochim Biophys Acta] Abstract

CHOP Favors Endoplasmic Reticulum Stress-Induced Apoptosis in Hepatocellular Carcinoma Cells via Inhibition of Autophagy

Investigators demonstrated the induction of endoplasmic reticulum stress in response to tunicamycin stimulation, as evidenced by increased expression of chaperone proteins Grp78, Grp94, and enhanced eukaryotic initiation factor 2 subunit 1 phosphorylation in hepatocellular carcinoma cells. [PLoS One] Full Article

miR-217 Targeting DKK1 Promotes Cancer Stem Cell Properties via Activation of the Wnt Signaling Pathway in Hepatocellular Carcinoma

Researchers demonstrated that miR-217 promoted the cancer stem cells-like phenotype via dickkopf-1 (DKK1) targeting, resulting in constitutive activation of Wnt signaling. Through real-time PCR, western blotting, luciferase assays, RNA immunoprecipitation, and in vitro and in vivo assays, they demonstrated that miR-217 expression was markedly increased in hepatocellular carcinoma tissues and cells. [Oncol Rep] Abstract

MiR-494 Upregulates the PI3K/Akt Pathway via Targeting PTEN and Attenuates Hepatic Ischemia/Reperfusion Injury in a Rat Model

The miR-494 target gene was identified by luciferase reporter assay, and verified both in vitro and in vivo experiments. MiR-494 protected rats against hepatic I/R injury through down-regulating its downstream target gene PTEN, leading to the activation of PI3K/AKT signaling pathway. [Biosci Rep] Abstract

SMARCD1 Regulates Senescence-Associated Lipid Accumulation in Hepatocytes

Researchers identified 16 senescence-associated genes by a subtractive proteomic analysis using presenescent and senescent human fibroblast cells, TIG-1. They clarified the role of SMARCD1, one of the identified genes, also known as BAF60a, in hepatic senescence. [NPJ Aging Mech Dis] Full Article

Epigenetics in Chronic Liver Disease

Elucidation of the fundamental epigenetic mechanisms governing gene expression and cellular phenotype in the past decade has provided novel insights into the epigenetic modulation of chronic liver disease. While genetic factors are undoubtedly important, the opportunity afforded by exploitation of the “fine-tuning” epigenetic mechanisms promises to drive forward an unprecedented advance in precision medicine within hepatology. [J Hepatol] Abstract

The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune Therapies

Significant progress has been made in uncovering genomic alterations in hepatocellular carcinoma, including potentially targetable aberrations. The most common molecular anomalies in this malignancy are mutations in the TERT promoter, TP53, CTNNB1, AXIN1, ARID1A, CDKN2A and CCND1 genes. [Mol Cancer] Full Article

Non-Alcoholic Fatty Liver Disease Promotes Hepatocellular Carcinoma through Direct and Indirect Effects on Hepatocytes

Inflammatory cytokines, ER stress and circadian dysregulation, which mediate hepatocyte injury and non-alcoholic fatty liver disease (NAFLD) progression, have been identified to promote malignant transformation of hepatocytes. The authors explore recent findings of both “intrinsic” effects on hepatocytes and the role of the local environment in NAFLD-promoted hepatocellular carcinoma development. [FEBS J] Full Article

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

Outstanding Investigator Grant Awarded to Dario C. Altieri, M.D., Wistar President and CEO

The Wistar Institute announced that distinguished scientist Dario C. Altieri, M.D., Wistar president and CEO and director of the Institute’s Cancer Center, has been awarded an Outstanding Investigator Grant by the National Institutes of Health for high-caliber research exploring “tumor plasticity.” This highly coveted NCI program grant totals nearly $8 million over seven years. [The Wistar Institute] Press Release

Dr. Peter Glazer Receives Prestigious Outstanding Investigator Award for Cancer Research

The National Cancer Institute has named Peter M. Glazer, M.D., Ph.D., as a recipient of its Outstanding Investigator Award. Glazer is the Robert E. Hunter Professor of Therapeutic Radiology, professor of genetics and chairman of the department of Therapeutic Radiology at Yale School of Medicine and Yale Cancer Center. [Yale School of Medicine] Press Release

FDA Warns US Stem Cell Clinic of Significant Deviations

The U.S. FDA posted a warning letter issued to US Stem Cell Clinic of Sunrise, Florida, and its Chief Scientific Officer Kristin Comella for marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. [U.S. Food and Drug Administration] Editorial

Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine

The FDA has taken steps in Florida and California to address a number of especially troubling products being marketed. But unfortunately, these are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk. [U.S. Food and Drug Administration] Editorial

Science Suffers as China’s Internet Censors Plug Holes in Great Firewall

China is tightening the screws on internet access, again. The latest crackdown—an evolving effort to ban virtual private networks not under government control—could seriously erode scientists’ ability to stay connected with peers abroad. [ScienceInsider] Editorial

NEW Keystone Symposia: Tumor Metabolism
January 21-25, 2018
Snowbird, Utah, United States

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NEW Postdoctoral Position – Cancer Biology (Georgetown University Medical Center)

Postdoctoral Position – Tumor Immunology and Metastasis (Vrije Universiteit Brussel)

Research Associate – Hepatitis B Virus Pathogenesis (Imperial College London)

Research Scientist – Chronic Fibrotic and Metabolic Diseases (Gilead Sciences, Inc.)

Research Fellows – Cancer Research (National University of Singapore)

Multiple Positions – Cancer Research (National University of Singapore)

Assistant Professor – Biomedical Research (National Institutes of Health)

Postdoctoral Scholar – Computational Biology/Cancer Genomics (University of Chicago)

Postdoctoral Fellow – Stem Cell Biology (University of Louisville)

Postdoctoral Research Fellow – Pathogenesis of Metabolic Diseases (Columbia University)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Translational Liver Cancer Research (Fred Hutchinson Cancer Research Center)

Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

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