Hepatic Cell News Volume 4.01 | Jan 17 2020

TOP STORY

TRIM25 Promotes the Cell Survival and Growth of Hepatocellular Carcinoma through Targeting Keap1-Nrf2 Pathway

Through the evaluation of all human TRIM proteins, investigators found that TRIM25 was significantly induced upon endoplasmic reticulum stress. Upregulation of TRIM25 ameliorated oxidative stress, promoted ER-associated degradation, and reduced IRE1 signaling in the UPR pathway. [Nat Commun] Full Article | Press Release

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SUMOylation Inhibitors Synergize with FXR Agonists in Combating Liver Fibrosis

Researchers report that prophylactic but not therapeutic administration of obeticholic acid (OCA) prevented hepatic stellate cell (HSCs) activation and fibrogenesis. Activated HSCs showed limited response to OCA and other farnesoid X receptor (FXR) agonists due to enhanced FXR SUMOylation. [Nat Commun] Full Article

Indoleamine 2, 3-Dioxygenase 1 Enhances Hepatocytes Ferroptosis in Acute Immune Hepatitis Associated with Excess Nitrative Stress

Consistent with the in vivo results, hepatocytes-specific knockdown of IDO1 led to ferroptosis resistance upon exposure to ferroptosis-inducing compound in vitro, whereas IDO1 overexpression aggravated the classical ferroptotic events, and the reactive nitrogen species stress. [Free Radic Biol Med] Abstract

Targeting Alkaline Ceramidase 3 Alleviates the Severity of Nonalcoholic Steatohepatitis by Reducing Oxidative Stress

Scientists found that alkaline ceramidase 3 (Acer3) mRNA levels and its enzymatic activity were also upregulated in mouse livers with nonalcoholic steatohepatitis induced by a palmitate-enriched Western diet. Moreover, they demonstrated that palmitate treatment also elevated Acer3 mRNA levels and its enzymatic activity in mouse primary hepatocytes. [Cell Death Dis] Full Article

Long Non-Coding RNA DLGAP1-AS1 Facilitates Tumorigenesis and Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma via the Feedback Loop of miR-26a/B-5p/IL-6/JAK2/STAT3 and Wnt/β-Catenin Pathway

Researchers attempted to elucidate the uncharacterized function and mechanism of lncRNA DLGAP1-AS1 in regulating tumorigenesis and epithelial–mesenchymal (EMT) transition of hepatocellular carcinoma (HCC). DLGAP1-AS1 was shown to be upregulated in HCC cell lines and capable to promote HCC progression and EMT. [Cell Death Dis] Full Article

Opposite Responses of Normal Hepatocytes and Hepatocellular Carcinoma Cells to Substrate Viscoelasticity

The authors studied the mechanoresponse of normal hepatocytes and hepatocellular carcinoma cells to elastic and viscoelastic substrates using the Huh7 cell line derived from a human liver tumor and primary human hepatocytes (PHH). Unlike PHH and fibroblasts, which responded to viscoelastic substrates by reducing spreading area and actin bundle assembly compared to purely elastic substrates of the same stiffness, Huh7 cells spread faster on viscoelastic substrates than on purely elastic substrates. [Biomater Sci] Abstract | Graphical Abstract

miR-552 Regulates Liver Tumor-Initiating Cells Expansion and Sorafenib Resistance

Functional studies revealed that a forced expression of miR-552 promoted liver T-ICs self-renewal and tumorigenesis. Conversely, miR-552 knockdown inhibited liver tumor-initiating cells self-renewal and tumorigenesis. Mechanistically, miR-552 downregulated PTEN via its mRNA 3’UTR and activates AKT phosphorylation. [Mol Ther Nucleic Acids] Abstract

McPip1 Inhibits Hepatitis B Virus Replication by Destabilizing Viral RNA and Negatively Regulates the Virus-Induced Innate Inflammatory Responses

Enforced monocyte chemotactic protein-induced protein 1 (MCPIP1) expression by hydrodynamic DNA injection in vivo significantly inhibited hepatitis B virus (HBV) replication in the mouse livers. In vitro studies by overexpression or knockdown assays in cell-lines, identified the direct antiviral effect of MCPIP1 on HBV replication. [Antiviral Res] Abstract

Induction of E6AP by microRNA-302c Dysregulation Inhibits TGF-β-Dependent Fibrogenesis in Hepatic Stellate Cells

Investigators examined whether E6 associated protein (E6AP) is overexpressed in activated hepatic stellate cells (HSCs), and if so, its effect on hepatic fibrogenesis and the molecular mechanism. E6AP was expressed higher in HSCs than hepatocytes, and was up-regulated in activated HSCs, HSCs from the livers of carbon tetrachloride-injected mice, or TGF-β-treated LX-2 cells. [Sci Rep] Full Article

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The Matrisome, Inflammation, and Liver Disease

The fibrotic stage of chronic liver disease is primarily characterized by robust accumulation of extracellular matrix (ECM) proteins that ultimately impairs the function of the organ. The role of the ECM in early stages of chronic liver disease is less well-understood, but recent research has demonstrated that several changes in the hepatic ECM in prefibrotic liver disease are not only present but may also contribute to disease progression. [Semin Liver Dis] Abstract

Developments in Predictive Biomarkers for Hepatocellular Carcinoma Therapy

The authors summarize the potential biological markers to predict the efficacy of all treatment available in patients with hepatocellular carcinoma and discuss a new biomarker with ahigher potential of success in the next future. [Expert Rev Anticancer Ther] Abstract

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URI Scientists Awarded $1.25 Million Grant to Provide Research Opportunities to Minority Students

Two scientists at the University of Rhode Island have been awarded a five-year, $1.25 million grant from the National Institutes of Health to encourage historically under-represented students to gain research experience in the biomedical sciences. [The University of Rhode Island] Press Release

Blue Faery Grants Liver Cancer Research Award

Blue Faery: The Adrienne Wilson Liver Cancer Association is proud to announce the annual Blue Faery Award for Excellence in Liver Cancer Research. Upon receiving the BFA Dr. Jinsil Seong stated, “I am truly honored and impressed to join world leaders in the hepatocellular carcinoma (HCC) field who won the award previously. This encourages me to keep going forward for [a] better future of our HCC patients!” [OncNursing] Press Release

Senate Bill Would Boost Spending on Trump Administration’s Research Priorities

A bipartisan group of senators asked the Trump administration to pump up funding for a handful of technologies they believe will drive future US economic growth. And the top White House technology officer thinks it’s a great idea. [ScienceInsider] Editorial

Florida Cracks Down on Foreign Government Involvement in Research

Florida is launching a statewide investigation into US research exploitation after four University of Florida faculty members and six employees of Moffitt Cancer Center in Tampa failed to disclose ties to foreign programs, reports the Tampa Bay Times. [The Scientist] Editorial

NEW The Microbiome and Viruses
February 21-24, 2020
Orlando, Florida, United States

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NEW Postdoctoral Fellow – Cell Therapy for Liver Repair (University of Edinburgh)

NEW Research Assistant – Gastroenterology Clinical Trials (Kingston General Hospital)

NEW Program Leader – Propionic Acidemia Research (Moderna)

Postdoctoral Fellow – Metabolic Dysfunction (Lewis Katz School of Medicine)

Postdoctoral Researchers – MicroRNAs in NAFLD (Weill Cornell Medicine)

Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

Research Associate – Liver Damage (University of Colorado Denver)

Postdoctoral Researcher – Cell Biology of the Liver (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Fellow – Liver Pathology (University of Illinois at Chicago)

Postdoctoral Researcher – HIV and the Liver (Seattle’s Children’s Hospital)

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