Hepatic Cell News Volume 2.40 | Oct 19 2018

TOP STORY

Nk Cell-Derived IFN-γ Promotes Hepatocellular Carcinoma through EpCAM-EMT Axis in Hepatitis B Virus Transgenic Mice

In hepatitis B virus transgenic mice, poly (I:C) induced liver inflammation with markedly increased infiltrating lymphocytes, along with the concurrently increased apoptosis and proliferation of hepatocytes, this led to accelerated epithelial-mesenchymal transition of hepatocytes shown by an increased expression of typical transcriptional factors and phenotypic proteins. [Hepatology] Abstract

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PRMT6 Regulates RAS/RAF Binding and MEK/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation

The authors found that protein methyltransferase 6 (PRMT6) was frequently downregulated in hepatocellular carcinoma (HCC) and its expression was negatively correlated with aggressive cancer features in HCC patients. Silencing of PRMT6 promoted the tumor-initiating, metastasis, and therapy resistance potential of HCC cell lines and patient-derived organoids. [Cell Rep] Full Article | Graphical Abstract

Carbon Monoxide-Induced TFEB Nuclear Translocation Enhances Mitophagy/Mitochondrial Biogenesis in Hepatocytes and Ameliorates Inflammatory Liver Injury

To investigate the effects of carbon monoxide (CO) on mitochondrial homeostasis in vivo, mice were treated with lipopolysaccharide (LPS)/D-galactosamine (D-GalN). CO inhalation reduced liver injury after challenge with LPS/GalN. CO inhalation increased transcription factor EB activation, mitophagy and mitochondrial biogenesis in mice treated with LPS/GalN. [Cell Death Dis] Full Article

Hepatitis C Virus-Infected Apoptotic Hepatocytes Program Macrophages and Hepatic Stellate Cells for Liver Inflammation and Fibrosis Development: Role of Ethanol as a Second Hit

After exposure to apoptotic bodies (AB) scientists observed activation of inflammasomes in monocyte-derived macrophages (MDMs), with a higher effect of AB hepatitis C virus(HCV)+, further enhanced by incubation of MDMs with ethanol. In hepatic stellate cells, activation of inflammasomes was modest; however, HCV and acetaldehyde-generating system exposure induced pro-fibrotic changes. [Biomolecules] Full Article

MicroRNA-302a/D Inhibits the Self-Renewal Capability and Cell Cycle Entry of Liver Cancer Stem Cells by Targeting the E2F7/AKT Axis

Investigators found that the miRNA-302 family was downregulated during the spheroid formation of hepatocellular carcinoma cells and patients with lower miRNA-302a/d expression had shorter overall survival and progression-free survival. E2F7 was confirmed to be directly targeted and inhibited by miRNA-302a/d. [J Exp Clin Cancer Res] Full Article

Small Heterodimer Partner Negatively Regulates C-X-C Motif Chemokine Ligand 2 in Hepatocytes during Liver Inflammation

Small heterodimer partner (SHP) deficiency in liver parenchymal cells was associated with increased susceptibility to concanavalin A (ConA)-induced hepatitis. Researchers also found SHP deficiency in liver parenchymal cells augmented neutrophil recruitment in ConA-induced hepatitis. [Sci Rep] Full Article

LINC01433 Promotes Hepatocellular Carcinoma Progression via Modulating the miR-1301/STAT3 Axis

It was exhibited that LINC01433 was remarkably elevated in hepatocellular carcinoma (HCC) cells, which indicated that LINC01433 was involved in HCC. Knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. [J Cell Physiol] Abstract

Emodin Sensitizes Hepatocellular Carcinoma Cells to the Anti-Cancer Effect of Sorafenib through Suppression of Cholesterol Metabolism

Scientists demonstrated that emodin significantly improved the anti-cancer effect of sorafenib in hepatocellular carcinoma cells, such as HepG2, Hep3B, Huh7, SK-HEP-1, and PLC/PRF5. Mechanistically, emodin inhibited sterol regulatory element-binding protein-2 transcriptional activity, which suppressed cholesterol biosynthesis and oncogenic protein kinase B signaling. [Int J Mol Sci] Full Article

4-Phenylbutyric Acid Attenuates Endoplasmic Reticulum Stress-Mediated Apoptosis and Protects the Hepatocytes from Intermittent Hypoxia-Induced Injury.

Intermittent hypoxia (IH) caused apoptosis in hepatocyte; IH caused endoplasmic reticulum stress (ERS) in hepatocyte, IH caused hepatic injury, 4-phenylbutyric acid (4-PBA) attenuated IH-induced liver cell injury, 4-PBA protected liver cell from IH-induced apoptosis, 4-PBA suppressed ERS-related apoptotic pathway, but did not suppress IH-induced unfold protein reaction. [Sleep Breath] Abstract

Cell Death in Cancer in the Era of Precision Medicine

In this review, authors briefly list some classes of target drugs (Bcl-2 family modulators, Tyrosine Kinase modulators, PARP inhibitors, and growth factors inhibitors) and discuss the application of immunotherapy in tumors (T cell-mediated immunotherapy and CAR-T cells) that in recent years has drastically changed the prognostic outlook of aggressive cancers. [Genes Immun] Abstract

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

uniQure Announces Development of a Highly Potent, Next-Generation Promoter for Liver-Directed Gene Therapies

uniQure presents non-clinical data demonstrating that a next-generation synthetic promoter developed for liver-directed gene therapy is able to drive gene expression at increased levels and with very high specificity, allowing uniQure to tailor expression levels required for a specific therapeutic transgene. [Press release from uniQure N.V. (GlobeNewswire, Inc.) discussing research presented at the 26^th Congress of the European Society of Gene and Cell Therapy, Lausanne.] Press Release

AbbVie and Morphic Therapeutic Announce Collaboration Targeting Fibrotic Diseases

AbbVie and Morphic Therapeutic, a biotechnology company developing oral integrin therapies, announced that the companies have entered into a research and development collaboration designed to advance a number of Morphic’s oral integrin therapeutics for fibrosis-related indications. [AbbVie Inc] Press Release

Delcath Announces Enrollment of First Patient in ALIGN Trial

Delcath Systems, Inc. announces that patient treatments have begun in the company’s second global US registration trial investigating Melphalan hydrochloride for injection for use with the Delcath Hepatic Delivery System in the treatment of patients with intrahepatic cholangiocarcinoma. [Delcath Systems Inc] Press Release

Alnylam Announces Plan to Initiate Rolling Submission of a New Drug Application and Pursue Full Approval for Givosiran

Alnylam Pharmaceuticals, Inc. announced that in consultation with the FDA, the company plans to pursue a full approval based on the complete results of the ENVISION Phase III study of givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 for the treatment of acute hepatic porphyria, rather than filing based on the interim Phase 3 results. [Alnylam Pharmaceuticals, Inc] Press Release

‘Vast Majority’ of NIH Chimps to Be Moved to Retirement Sanctuary, Agency Says

The National Institutes of Health (NIH) plans to move the “vast majority” of its chimpanzees formerly used for research to a sanctuary in Louisiana, Director Francis Collins told STAT. The NIH released a slate of decisions Thursday laying out its plans for the hundreds of chimps that are still living in agency-supported research facilities. [STAT News] Editorial

‘We Are Headed for a Very Dark Period.’ Brazil’s Researchers Fear Election of Far-Right Presidential Candidate

Beset by economic woes and dissatisfied with the left-wing politicians in power for most of the past 15 years, Brazil appears poised to make a hard turn and elect a far-right candidate, Jair Bolsonaro, as its next president. His rapid ascent has unnerved local researchers, who worry about the future of Brazilian science, the protection of the country’s biodiversity, and its role in the global struggle against climate change. [ScienceInsider] Editorial

NEW Global NASH Congress
February 25-26, 2019
London, United Kingdom

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

NEW Principal Scientific Officer – Liver Regeneration & Cancer (Cancer Research UK Beatson Institute)

Postdoctoral Researcher – RNA-Targeting Therapeutics (Ionis Pharmaceuticals, Inc.)

Research Fellow – Antibody Engineering and Hepatitis B Virology (National University of Singapore)

Postdoctoral Fellow – Inflammation/Innate Immunity/Cell Signaling (University of Colorado Denver)

Principal Investigator/Group Leader in Non-Alcoholic Fatty Liver Disease (Foundation for Liver Research)

Assistant Professor – Faculty Positions in Basic and Translational Cancer Research (Texas Tech University Health Sciences Center)

Post-Doctoral Position – Liver Research (University of Pittsburgh Drug Discovery Institute)

Group Leader – Organoid Modeling of Disease (European Molecular Biology Laboratory)

Faculty Position – Biochemistry and/or Biophysics (University of Kansas Medical Center)

Faculty Position – Cancer Biology (Children’s Research Institute at UT Southwestern)

Principal Investigator/Group Leader – Non-Alcoholic Fatty Liver Disease (Foundation for Liver Research)

Postdoctoral Scholarship – Diabetes and Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

Postdoctoral Biomedical Engineer – Human Liver Microphysiology Systems (University of Pittsburgh Drug Discovery Institute)

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