Hepatic Cell News Volume 2.14 | Apr 20 2018

TOP STORY

Squalene Epoxidase Drives NAFLD-Induced Hepatocellular Carcinoma and Is a Pharmaceutical Target

RNA sequencing analysis of nonalcoholic fatty liver disease (NAFLD)-hepatocellular carcinoma (HCC) samples revealed squalene epoxidase (SQLE) as the top outlier metabolic gene overexpressed in NAFLD-HCC patients. Increased SQLE expression promoted the biosynthesis of cholesteryl ester, which induced NAFLD-HCC cell growth. [Sci Transl Med] Abstract | Press Release

(Ranked by impact factor of the journal)

The LINC01138 Drives Malignancies via Activating Arginine Methyltransferase 5 in Hepatocellular Carcinoma

Researchers characterized an oncogenic long intergenic non-coding RNA in the frequent DNA-gain regions in hepatocellular carcinoma (HCC), LINC01138. LINC01138 acted as an oncogenic driver that promotes cell proliferation, tumorigenicity, tumor invasion and metastasis by physically interacting with arginine methyltransferase 5 and enhancing its protein stability by blocking ubiquitin/proteasome-dependent degradation in HCC. [Nat Commun] Full Article

Hepatocellular Carcinoma-Associated Protein TD26 Interacts and Enhances SREBP1 Activity to Promote Tumor Cell Proliferation and Growth

Investigators showed that hepatocellular carcinoma-associated protein TD26 (TD26) was highly expressed in hepatocellular carcinoma (HCC) tumor tissues compared to matched normal tissues. Their functional assays indicate that TD26 promoted HCC cell proliferation and tumor growth. [Hepatology] Abstract

The AMPK-V-ATPase-pH Axis: A Key Regulator of the Pro-Fibrogenic Phenotype of Human Hepatic Stellate Cells

Scientists investigated the functional role of vacuolar H⁺ adenosine‐tri‐phosphatase in primary human hepatic stellate cells activation and its modulation by specific AMPK subunits. [Hepatology] Abstract

Liver-Targeted Anti-HBV Single-Stranded Oligonucleotides with Locked Nucleic Acid Potently Reduce HBV Gene Expression In Vivo

The authors describe a hepatitis B virus (HBV)-specific locked nucleic acid (LNA)-single-stranded oligonucleotide that effectively reduces intracellular viral mRNAs and viral antigens over an extended time period in cultured human hepatoma cell lines that were infected with HBV with mean 50% effective concentration values ranging from 1.19 to 1.66 μM. [Mol Ther Nucleic Acids] Full Article

Genetic and Phenotypic Difference in CD8⁺ T Cell Exhaustion between Chronic Hepatitis B Infection and Hepatocellular Carcinoma

Investigators assayed the phenotypes and functional states of CD8⁺ T cells separating from human chronic hepatitis B (CHB) tissues and hepatocellular carcinoma (HCC) tissues. Compared with CD8⁺ T cells from CHB tissues, those from HCC tissue showed higher expression levels of exhaustion markers, lower levels of proliferation, cell activity and the production of effector cytokines. [J Med Genet] Full Article

Exosomal circRNA_100284 from Arsenite-Transformed Cells, via MicroRNA-217 Regulation of EZH2, Is Involved in the Malignant Transformation of Human Hepatic Cells by Accelerating the Cell Cycle and Promoting Cell Proliferation

Researchers showed that circular RNAs (circRNA)_100284 is involved in the malignant transformation of L-02 cells induced by arsenite. Exosomes derived from transformed L-02 cells transferred circRNA_100284 to surrounding cells, which induced an accelerated cell cycle and promoted proliferation of normal liver cells and led to the malignant transformation of the non-transformed cells. [Cell Death Dis] Abstract

Sp1-Regulated Transcription of RasGRP1 Promotes HCC Proliferation

The authors evaluated the expression of Ras guanine nucleotide releasing protein 1 (RasGRP1) in hepatocellular carcinoma (HCC) and determined how it contributes to HCC cell proliferation. [Liver Int] Abstract

Characterization of the Most Frequent ATP7B Mutation Causing Wilson Disease in Hepatocytes from Patient Induced Pluripotent Stem Cells

Scientists reprogrammed skin fibroblasts of homozygous ATP7B-H1069Q patients into induced pluripotent stem cells and differentiated them into hepatocyte-like cells. [Sci Rep] Full Article

Radiosensitization by Marine Sponge Agelas sp. Extracts in Hepatocellular Carcinoma Cells with Autophagy Induction

Six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity. Two extracts derived from Agelas sponges collected off the coast of Kosrae and Chuuk, the Federated States of Micronesia significantly decreased clonogenic survival of hepatocellular carcinoma cells after exposure to ionizing radiation. [Sci Rep] Full Article

Slit2-Robo2 Signaling Modulates the Fibrogenic Activity and Migration of Hepatic Stellate Cells

The authors investigated the functional significance of Slit/Robo signaling in liver fibrogenesis and in hepatic stellate cells. [Life Sci] Abstract

Exosomal miRNAs in Hepatocellular Carcinoma Development and Clinical Responses

Scientists summarize the latest findings between exosomal miRNAs and hepatocellular carcinoma (HCC), in order to better comprehend the functions and applications in HCC. They discuss critical issues to consider when developing anti-tumor exosomal miRNAs as a novel therapeutic strategy for treating HCC in the clinic. [J Hematol Oncol] Full Article

Liver Fibrosis: Direct Antifibrotic Agents and Targeted Therapies

Researchers discuss targeted antifibrotic therapies that address molecules and mechanisms that are central to fibrogenesis or fibrolysis, including strategies that allow targeting of activated hepatic stellate cells and myofibroblasts and other fibrogenic effector cells. [Matrix Biol] Abstract

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

NGM Bio Announces Results from Phase II Study of NGM282 In NASH Patients Demonstrating Clinically Significant Improvements in Liver Histology after 12 Weeks

NGM Bio announced data from a Phase II study of its lead product candidate, NGM282, demonstrating clinically meaningful improvements in histological measures of disease in nonalcoholic steatohepatitis (NASH) patients at twelve weeks. [Press release from NGM Bio discussing research presented at The International Liver Congress 2018, Paris] Press Release

Dr. Tamara Zietek discusses the use of intestinal organoids as a model system for nutrient transport. Listen Now

Bioatla Announces FDA Clearance of Investigational New Drug Application for CAB-ROR2-ADC Therapeutic

BioAtla, LLC announced the FDA has cleared BioAtla’s Investigational New Drug application for BA3021, a first-in-class conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC), in patients with solid tumors. [BioAtla, LLC (PR Newswire Association LLC.)] Press Release

VBI Vaccines Announces Completion of Enrollment in PROTECT Phase III Clinical Study for Sci-B-Vac^® Hepatitis B Vaccine

VBI Vaccines Inc. announced the completion of enrollment with the last patient receiving the first dose in the ongoing PROTECT Phase III study of Sci-B-Vac^®, the company’s third-generation hepatitis B vaccine. [VBI Vaccines Inc.] Press Release

Nektar Announces Dosing of First Patient in Phase I/II Clinical Study to Evaluate Combination of TLR Agonist NKTR-262 with CD122-Biased Agonist NKTR-214 in Patients with Advanced Solid Tumors

Nektar Therapeutics announced that it has initiated dosing patients in the Phase I/II REVEAL clinical study evaluating the efficacy and safety of the combination of investigational medicines NKTR-262 and NKTR-214 in the treatment of solid tumors. [Nektar Therapeutics] Press Release

Dutch Universities, Journal Publishers Agree on Open-Access Deals

Despite some difficult negotiations, academic institutions in the Netherlands have been securing subscriptions that combine publishing and reading into one fee. [The Scientist] Editorial

African Scientists Call for More Control of Their Continent’s Genomic Data

Africa-based researchers issued guidelines for the ethical handling of samples for genomic studies. The voluntary rules are an effort to combat ‘helicopter’ research, in which foreign scientists take samples and data from communities and then return to their home institutions. [Nature News] Editorial

Women Less Successful When Applying for Patents

Women inventors have less success than men at each step of the patent application process in the U.S., according to a study published this month in Nature Biotechnology. [The Scientist] Editorial

NEW Industry Colloquium: Novel Targets and Therapies in Liver Disease
October 19-20, 2018
Rockville, Maryland, United States

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

NEW PhD Student – Hepatology and Cancer Biology (German Cancer Research Center (DKFZ))

Postdoctoral Researcher – Liver Cancer and Epigenetics (International Clinical Research Center)

Research Fellow – Liver Tumorigenesis (Harvard School of Dental Medicine)

Postdoctoral Fellow – Alcoholic Liver Disease (University of North Carolina at Greensboro)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Assistant/Associate Professor – Virology (Saint Louis University School of Medicine)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

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

Postdoctoral Fellow – Human Liver Function (Karolinska Institutet)

Postdoctoral Research Associate – Hepatitis B Virology (Imperial College London)

Postdoctoral Research Associate – Liver Diseases (University of Illinois at Chicago)

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