Hepatic Cell News Volume 4.05 | Feb 14 2020

TOP STORY

Fasting-Induced FGF21 Signaling Activates Hepatic Autophagy and Lipid Degradation via JMJD3 Histone Demethylase

Researchers report fasting-induced fibroblast growth factor-21 (FGF21) signaling activates hepatic autophagy and lipid degradation via Jumonji-D3 (JMJD3) histone demethylase. Upon FGF21 signaling, JMJD3 epigenetically upregulated global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. [Nat Commun] Full Article

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NOTCH Target Gene HES5 Mediates Oncogenic and Tumor Suppressive Functions in Hepatocarcinogenesis

Investigators functionally characterized the NOTCH target HES5 and the patient-derived HES5-R31G mutation in vitro and in an orthotopic mouse model applying different oncogenic backgrounds, to dissect the role of HES5 in different tumor subgroups in vivo. They identified nonsynonymous mutations in 14 immediate NOTCH pathway genes affecting 24.1% and 16.8% of hepatocellular carcinoma patients in the two independent cohorts, respectively. [Oncogene] Full Article

An Organoid-Based Carcinogenesis Model Induced by In Vitro Chemical Treatment

To establish an organoid-based chemical carcinogenesis model, mouse organoids were treated in vitro with 4 genotoxic chemicals, e.g., ethyl methanesulfonate, acrylamide, diethylnitrosamine and 7,12-dimethylbenz[a]anthracene to examine their tumorigenicity after injection to nude mice. [Carcinogenesis] Abstract

Nandrolone Induces a Stem Cell-Like Phenotype in Human Hepatocarcinoma-Derived Cell Line Inhibiting Mitochondrial Respiratory Activity

The authors investigated the impact of nandrolone on the metabolic phenotype in a HepG2 cell line. The results attained show that pharmacological dosage of nandrolone, slowing cell growth, repressed mitochondrial respiration, inhibited the respiratory chain complexes I and III and enhanced mitochondrial reactive oxygen species production. [Sci Rep] Full Article

Obg-Like ATPase 1 (OLA1) Overexpression Predicts Poor Prognosis and Promotes Tumor Progression by Regulating P21/CDK2 in Hepatocellular Carcinoma

High expression of OLA1 in hepatocellular carcinoma (HCC) was detected in public datasets and clinical samples, and correlated with poor prognosis. Downregulation of OLA1 significantly inhibited the proliferation, migration, invasion and tumorigenicity of HCC cells. [Aging (Albany NY)] Full Article

Orlistat Delays Hepatocarcinogenesis in Mice with Hepatic Co-Activation of AKT and C-Met

Researchers assessed the antisteatotic and antitumorigenic efficacy of orlistat in a rapid HCC FVB/N mouse model established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Human hepatoma cell lines were used for mechanical validation in vitro. [Toxicol Appl Pharmacol] Abstract

Circular RNA-0072309 Has Antitumor Influences in Hep3B Cell Line by Targeting MicroRNA-665

The Hep3B cell line was transfected with pc-circ and si-circ for viability, colony formation, apoptosis, migration, and invasion tests, which were individually performed by CCK-8, colony formation detection, flow cytometry assay, migration and invasion assays. The luciferase reporter assay was conducted to determine the target relationship between the circRNA-0072309 and miR-665. [Biofactors] Abstract

Investigation of Possible Effects of Apigenin, Sorafenib and Combined Applications on Apoptosis and Cell Cycle in Hepatocellular Cancer Cells

Scientists investigated the combined therapeutic effects of sorafenib and apigenin upon apoptosis and cell cycle on the HepG2 cell line. Cytotoxic effects of sorafenib and apigenin on HepG2 cells were determined by XTT assay. Effects of single and combined treatment on cell migration, invasion and colony formation were analyzed by wound healing, transwell matrigel invasion assay and colony formation assay, respectively. [Gene] Abstract

Downregulated Long Non-Coding RNA LINC01093 in Liver Fibrosis Promotes Hepatocyte Apoptosis via Increasing Ubiquitination of SIRT1

Investigators identified whether SIRT1 was regulated by long non-coding RNA LINC01093 and explored its underlying mechanisms. Liver fibrosis was induced in mice using CCl⁴, and the differential expressions of several fibrosis-related lncRNAs were detected in liver tissues. [J Biochem] Abstract

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MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease

A group of experts sought to integrate the current understanding of patient heterogeneity captured under the acronym nonalcoholic fatty liver disease (NAFLD) and provide suggestions on terminology that more accurately reflects pathogenesis and can help in patient stratification for management. [Gastroenterology] Abstract

Human Antigen R: A Potential Therapeutic Target for Liver Diseases

The authors introduce the function and mechanistic characterization of human antigen R (HuR), and then focus on the physiopathological roles of HuR in the development of different liver diseases, including hepatic inflammation, alcoholic liver diseases, non-alcoholic fatty liver diseases, viral hepatitis, liver fibrosis and liver cancers. [Pharmacol Res] Abstract | Graphical Abstract

Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. Investigators provide an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases. [Cells] Abstract | Download Full Article | Graphical Abstract

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Last Patient Last Visit in Cyclo Therapeutics’ Phase I Trial in Niemann-Pick Type C

Cyclo Therapeutics, Inc. announced that the last patient has undergone the final assessment in its Phase I trial to evaluate the safety and tolerability of Trappsol^® Cyclo™ administered intravenously to Niemann-Pick Disease Type C patients. [Cyclo Therapeutics, Inc.] Press Release

Sirnaomics’ siRNA Therapeutic Candidate, STP705, Granted Orphan Drug Designation By US FDA for Treatment of Hepatocellular Carcinoma

Sirnaomics, Inc. announced that the Office of Orphan Product Development division of the FDA has granted orphan drug designation to its leading therapeutic candidate, STP705, for the treatment of hepatocellular carcinoma. [Sirnaomics, Inc.] Press Release

Harvard, Yale Investigated for Undisclosed Foreign Funding

The US Department of Education is investigating Harvard and Yale Universities for allegedly failing to disclose funds from other nations, according to a statement released February 12. First reported by the Wall Street Journal on Wednesday, the investigations are the latest in a series of efforts by the department to crack down on foreign influence in US institutions. [The Scientist] Editorial

Popular Preprint Servers Face Closure Because of Money Troubles

The rise of preprint repositories has helped scientists worldwide to share results and get feedback quickly. But several platforms that serve researchers in emerging economies are struggling to raise money to stay afloat. Repositories like INA-Rxiv and IndiaRxiv boost regional science, but finding cash to run them is proving difficult. [Nature News] Editorial

FDA Now Allows Certain Lab Animals to Be Retired and Adopted

The US Food and Drug Administration will now permit certain animals used in experiments to retire and be adopted rather than face euthanasia, according to internal documents reviewed by The Hill. Although the policy changed in November, there have not been any public statements from the agency. [The Scientist] Editorial

NEW American Association for Cancer Research (AACR) Annual Meeting 2020
April 24-29, 2020
San Diego, California, United States

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

NEW Network Manager – Non-Alcoholic Liver Disease (Hans-Knöll-Institute)

Postdoctoral Fellow – Fatty Liver Dieases (University of Kansas Medical Center)

Postdoctoral Fellow – Diabetes and Fatty Liver Disease (NIH National Heart, Lung, and Blood Institute)

Postdoctoral Position – Culturing ‘Foie Gras’ (KU Leuven)

Team Leader – Cholangiocytes (Miromatrix Medical)

Program Leader – Propionic Acidemia Research (None)

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)

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