Hepatic Cell News Volume 2.39 | Oct 12 2018

TOP STORY

PI3Kδ Is a New Therapeutic Target in Hepatocellular Carcinoma

The authors established a chemical carcinogenesis model of liver malignancy, which reflects the malignant phenotype and the in vivo environment of advanced hepatocellular carcinoma (HCC) cells. In this in vivo advanced HCC-mimic system using HCC-cells treated with H₂ O₂, they showed that H₂ O₂ selectively increased class I phosphoinositide 3-kinase (PI3K) activity while decreasing that of other class I PI3Ks. [Hepatology] Abstract

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iNOS Promotes CD24⁺CD133⁺ Liver Cancer Stem Cell Phenotype through a TACE/ADAM17-Dependent Notch Signaling Pathway

The expression of nitric oxide synthase in CD24⁺CD133⁺ liver cancer stem cells (LCSCs), but not CD24^–CD133⁻ LCSCs, promoted Notch1 signaling and stemness characteristics in vitro and in vivo, as well as accelerating hepatocellular carcinoma initiation and tumor formation in the mouse xenograft tumor model. [Proc Natl Acad Sci USA] Full Article

Long Non-Coding RNA PVT1 Promotes Cell Proliferation and Migration by Silencing ANGPTL4 Expression in Cholangiocarcinoma

the authors found that the long non-coding RNA PVT1, whose expression is significantly elevated in cholangiocarcinoma, could be a molecular marker of cholangiocarcinoma. They indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA-seq analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation and the apoptotic process. [Mol Ther Methods Clin Dev] Full Article

Suppressor of Hepatocellular Carcinoma RASSF1A Activates Autophagy Initiation and Maturation

Scientists tested whether ras association domain family 1 isoform A itself functions as a hepatocellular carcinoma (HCC) suppressor and activates autophagy similarly as microtubule-associated protein 1S does. They showed that RASSF1A deletion led to an acceleration of diethylnitrosamine-induced HCC and a 31% reduction of median survival times in mice. [Cell Death Differ] Abstract

Oleanolic Acid Inhibits Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Promoting iNOS Dimerization

Scientists demonstrated that oleanolic acid (OA) attenuated migration and invasion abilities, resulting in the suppression of the epithelial-mesenchymal transition process in liver cancer cells, and inhibited the tumor growth of PLC-bearing mice. They further proved that inducible nitric oxide synthase may be the potential target of OA. [Mol Cancer Ther] Full Article

miR-126 Negatively Regulates PLK-4 to Impact the Development of Hepatocellular Carcinoma via ATR/CHEK1 Pathway

Investigators found that miR-126 was downregulated both in hepatocellular carcinoma tissues and cell lines. Low expression level of miR-126 was associated with poor overall survival, late TNM stage and the presence of recurrence. Overexpression of miR-126 significantly decreased cell proliferation, metastasis and promoted apoptosis in vitro. Additional, high miR-126 expression reduced the tumor growth in vivo. [Cell Death Dis] Full Article

Modeling Liver Cancer and Therapy Responsiveness Using Organoids Derived from Primary Mouse Liver Tumors

The authors succeeded in culturing 91 lines from 129 liver tissue/tumors. These organoids were then grown in long-term cultures in vitro. About 20% of these organoids formed tumors in immunodeficient mice upon (serial) transplantation, confirming their tumorigenic and self-renewal properties. [Carcinogenesis] Abstract

Effect of SEPT6 on the Biological Behavior of Hepatic Stellate Cells and Liver Fibrosis in Rats and Its Mechanism

Scientists demonstrated that SEPT6 expression was significantly elevated following the activation of primary rat hepatic stellate cells (HSCs), the human hepatic stellate cell line LX-2 and the rat hepatic stellate cell line HSC-T6, as well as in both human and rat fibrotic liver tissue. [Lab Invest] Abstract

CHI3L1 Promotes Tumor Progression by Activating TGF-β Signaling Pathway in Hepatocellular Carcinoma

Researchers showed that, both in vivo and in vitro, overexpression of CHI3L1 (YKL40) could promote liver cancer cell growth, migration and invasion. They used RNA-seq to analyze the expression profiles of CHI3L1 overexpressed in two HCC cell lines and found that CHI3L1 overexpression affected genes that were involved in cell-cell adhesion, extracellular exosome and adherens junction. [Sci Rep] Full Article

Secondary Unconjugated Bile Acids Induce Hepatic Stellate Cell Activation

Researchers conducted a comprehensive DNA microarray study of the human hepatic stellate cell (HSC) line LX-2 treated with deoxycholic acid, a secondary unconjugated bile acid. Additionally, LX-2 cells were exposed to nine bile acids and studied using immunofluorescence staining, enzyme-linked immunosorbent assay, and flow cytometry to examine the mechanisms of HSC activation. [Int J Mol Sci] Full Article

Overexpression of CXCL2 Inhibits Cell Proliferation and Promotes Apoptosis in Hepatocellular Carcinoma

Investigators found that C-X-C motif chemokine ligand 2 (CXCL2) expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. [BMB Rep] Abstract

Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression from NAFLD to NASH

The pathogenesis of nonalcoholic fatty liver disease and the mechanisms behind its progression to nonalcoholic steatohepatitis have been extensively studied. While the processes that determine fat accumulation are mostly clear, the mechanisms associated with the progression of the disease are not fully characterized. [Transplantation] Abstract

Gut Microbiota’s Relationship with Liver Disease and Role in Hepatoprotection by Dietary Natural Products and Probiotics

A variety of dietary natural products have shown hepatoprotective effects. Increasing evidence has also demonstrated that gut microorganisms play an important role in the hepatoprotection contributed by natural products. [Nutrients] Full Article

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£2.3M Awarded for Liver Research Trial

Dr Mark McPhail from the Department of Inflammation Biology, School of Immunology & Microbial Sciences and Dr Vishal Patel from the Institute of Liver Studies at King’s College Hospital have been awarded £2.3 million by the National Institute for Health Research Health Technology Assessment to lead a new UK wide multi-centre trial to treat liver disease. [King’s College London] Press Release

Arix Bioscience Plc: Pharmaxis Releases Positive Results of Phase I Clinical Trial for LOXL2 Inhibitor Compound

Pharmaxis Ltd announced positive results from the Phase I clinical trial for the first of its Lysyl Oxidase Like 2 (LOXL2) inhibitor compounds being developed to treat fibrotic diseases such as Non-Alcoholic Steatohepatitis and Idiopathic Pulmonary Fibrosis. [Pharmaxis Ltd] Press Release

Surging R&D Spending in China Narrows Gap with United States

China’s total spending on R&D rose a robust 12.3% last year to a record 1.76 trillion yuan ($254 billion), according to a government report. Already second in the world in R&D spending behind the United States, China has narrowed the gap. [ScienceInsider] Editorial

Ghost Authorship Haunts Industry-Funded Clinical Trials

An analysis of industry-funded clinical trials has found that drug companies are often heavily involved in research — but are not always transparent about it. [Nature News] Editorial

NEW International Society for Stem Cell Research (ISSCR) 2019 Annual Meeting
June 26-29, 2019
Los Angeles, California, United States

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

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

NEW 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)

Postdoctoral Scholar, Microbiology and Immunology (Penn State College of Medicine)

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)

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

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