Vol. 5.36 – 24 September, 2021 TOP STORY Inhibition of ATG3 Ameliorates Liver Steatosis by Increasing Mitochondrial Function By performing a liver proteomic analysis from mice with genetic manipulation of hepatic p63, a regulator of fatty acid metabolism, investigators identified autophagy-related gene 3 (ATG3) as a new target downstream of p63. [Journal of Hepatology] Full ArticleGraphical Abstract PUBLICATIONSRanked by the impact factor of the journal The Transcription Factor ZHX2 Alleviates Nonalcoholic Steatohepatitis by Transcriptional Activation of PTEN Researchers identified a transcription factor Zinc Fingers and Homeoboxes 2 (ZHX2) in hepatocytes as a protective factor against steatohepatitis. Hepatocyte-specific ablation of ZHX2 exacerbated NASH-related phenotypes in mice, including lipid accumulation, enhanced inflammation, and hepatic fibrosis. [Hepatology] Abstract Integration of Feeding Behavior by the Liver Circadian Clock Reveals Network Dependency of Metabolic Rhythms Scientists isolated the interaction between feeding and the liver clock by reconstituting Bmal1 exclusively in hepatocytes, in otherwise clock-less mice, and controlling timing of food intake. [Science Advances] Full Article Genetic and Epigenetic Basis of Hepatoblastoma Diversity The authors performed integrative genomic profiling of 163 pediatric liver tumors based on the data acquired from a cohort study. DNA methylation profiling revealed that classical hepatoblastomas were characterized by the specific hypomethylated enhancers, which were enriched with binding sites for ASCL2, a regulatory transcription factor for definitive endoderm in Wnt-pathway. [Nature Communications] Full Article FSTL1 Secreted by Activated Fibroblasts Promotes Hepatocellular Carcinoma Metastasis and Stemness Investigators showed follistatin-like 1 (FSTL1) expression to be closely correlated with activated fibroblasts and to be elevated in regenerative, fibrotic, and disease liver states in various mouse models. Consistently, FSTL1 lineage cells gave rise to myofibroblasts in a CCL4-induced hepatic fibrosis mouse model. [Cancer Research] Abstract Sphingosine-1-Phosphate Transporter Spinster Homologue 2 Is Essential for Iron-Regulated Metastasis of Hepatocellular Carcinoma In addition to hepatocellular carcinoma (HCC) cell lines and clinical samples in vitro, iron deficient mouse models were generated using iron-free diet and transferrin receptor protein knock out, followed by administration of HCC tumors through either orthotopic or ectopic route. [Molecular Therapy] AbstractGraphical Abstract LNCAROD Enhances Hepatocellular Carcinoma Malignancy by Activating Glycolysis through Induction of Pyruvate Kinase Isoform PKM2 Scientists found that LNCAROD was significantly upregulated and predicted a poorer prognosis in hepatocellular carcinoma (HCC) patients. LNCAROD significantly promoted HCC cell proliferation, migration, invasion, and chemoresistance both in vitro and in vivo. [Journal of Experimental & Clinical Cancer Research] Full Article The LIN28B/TGF-β/TGFBI Feedback Loop Promotes Cell Migration and Tumor Initiation Potential in Cholangiocarcinoma Researchers found that the RNA-binding protein LIN28B, a known regulator of microRNA biogenesis, stem cell maintenance, and oncogenesis, was expressed in a subpopulation of cholangiocarcinoma patients. [Cancer Gene Therapy] Full Article Kruppel-Like Factor 15 Induces the Development of Mature Hepatocyte-Like Cells from Hepatoblasts Kruppel-like factor 15 (KLF15) was identified as a new regulator of hepatic maturation through a comprehensive analysis of the expression of transcriptional regulators in mouse fetal and adult hepatocytes. [Scientific Reports] Full Article Macrophage Autophagy Protects against Hepatocellular Carcinogenesis in Mice The authors investigated whether macrophage autophagy may have protected against hepatocellular carcinoma. In vitro studies demonstrated that hepatoma cells impaired the autophagy flux of macrophages and stimulated their expression of programmed cell death-ligand 1, a major regulator of the immune checkpoint. [Scientific Reports] Full Article O-GlcNAcylation Inhibits Hepatic Stellate Cell Activation Researchers aimed to evaluate the role of O-GlcNAc transferase (OGT) in hepatic stellate cells (HSCs) and its consequent role in liver fibrosis. RNA-seq showed that OGT knockdown in HSCs modulated key signaling pathways involved in HSC activation. [Journal of Gastroenterology and Hepatology] Abstract Gut Microbiota Depletion Exacerbates Cholestatic Liver Injury via Loss of FXR Signaling Investigators identified a role for microbiota-dependent changes in bile acid (BA) synthesis that modulated primary sclerosing cholangitis (PSC) pathophysiology. They showed that loss of microbiota-mediated negative feedback control of BA synthesis resulted in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. [Nature Metabolism] Abstract REVIEWS Dysregulation of Non-Coding RNAs Mediates Cisplatin Resistance in Hepatocellular Carcinoma and Therapeutic Strategies The authors highlight the regulatory roles of non-coding RNAs in cisplatin (CDDP) resistance of hepatocellular carcinoma (HCC), elucidate the multiple potential mechanisms by which HCC develops CDDP resistance, and attempt to propose multiple drug delivery systems to alleviate CDDP resistance. [Pharmacological Research] AbstractGraphical Abstract The Role of Hepatic Lipid Composition in Obesity-Related Metabolic Disease Scientists summarize cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterize hepatic lipid composition in people with obesity and related metabolic disease. [Liver International] AbstractFull Article INDUSTRY AND POLICY NEWS Mirum Pharmaceuticals and Takeda Enter into Exclusive Licensing Agreement to Develop and Commercialize Maralixibat for Rare Pediatric Liver Diseases in Japan Mirum Pharmaceuticals, Inc. and Takeda Pharmaceutical Company Limited announced that the companies have entered into an exclusive licensing agreement for the development and commercialization of maralixibat in Japan for Alagille syndrome, progressive familial intrahepatic cholestasis, and biliary atresia. [Mirum Pharmaceuticals, Inc.] Press Release Poxel Completes Enrollment in Phase II NASH Trial for PXL065 (DESTINY-1) in Biopsy-Proven Patients POXEL SA announced the completion of enrollment in DESTINY-1, a dose-ranging Phase II trial evaluating PXL065 for the treatment of non-alcoholic steatohepatitis (NASH). [POXEL SA] Press Release Tempest Announces First Patient Dosed in Randomized Study Evaluating TPST-1120 in First-Line Regimen for Hepatocellular Carcinoma in Clinical Collaboration with Roche Tempest Therapeutics, Inc. announced the first patient has been dosed in the global randomized Phase Ib/II clinical study evaluating TPST-1120, Tempest’s small molecule PPAR⍺ antagonist, in combination with the standard-of-care regimen of atezolizumab and bevacizumab in the first-line treatment of patients with advanced or metastatic hepatocellular carcinoma. [Tempest Therapeutics, Inc.] Press Release FEATURED EVENT Cell-NCI Symposium: Beyond Cancer Genomics Toward Precision Oncology October 4 – 6, 2021 Virtual > See All Events JOB OPPORTUNITIES Research Assistant – Regenerative Medicine for the Biliary System University of Cambridge – Cambridge, England, United Kingdom Scientist – Endocrine Disease Specialist Novo Nordisk – Indianapolis, Indiana, United States Faculty Position – Hepatology Researcher, Department of Medicine UConn Health – Farmington, Connecticut, United States Senior Scientific Officer – Cancer Cells in Metastatic Microenvironments CRUK Beatson Institute for Cancer Research – Glasgow, Scotland, United Kingdom Postdoctoral Positions – Organ Cross-Talk and Metabolic Disorders European Centre Study Diabetes – Strasbourg, France > See All Jobs Brought to you by Science News Hepatic Cell News Archives Contact Us