Hepatic Cell News Volume 1.18 | Jun 2 2017

TOP STORY

The MBNL3 Splicing Factor Promotes Hepatocellular Carcinoma by Increasing PXN Expression through the Alternative Splicing of LncRNA-PXN-AS1

Scientists identified an oncofetal splicing factor, MBNL3, which promoted tumorigenesis and indicated poor prognosis of hepatocellular carcinoma patients. MBNL3 knockdown almost completely abolished hepatocellular carcinoma tumorigenesis. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

Downregulation of SIRT1 Signaling Underlies Hepatic Autophagy Impairment in Glycogen Storage Disease Type Ia

The authors showed that in mice, liver-specific knockout of glucose-6-phosphatase-α lead to downregulation of sirtuin 1 (SIRT1) signaling that activated autophagy via deacetylation of autophagy-related proteins and forkhead box O family of transcriptional factors which transactivate autophagy genes. [PLoS Genet] Full Article

Efficacy of AKT Inhibitor ARQ 092 Compared with Sorafenib in a Cirrhotic Rat Model with Hepatocellular Carcinoma

Researchers assessed efficacy of the allosteric AKT inhibitor ARQ 092 compared to untreated control and to standard treatment, sorafenib, in vitro and in vivo. ARQ 092 blocked phosphorylation of AKT in vitro and strongly inhibited cell growth with significantly higher potency than sorafenib. [Mol Cancer Ther] Abstract

α2,6-Sialylation Mediates Hepatocellular Carcinoma Growth In Vitro and In Vivo by Targeting the Wnt/β-Catenin Pathway

Investigators found that ST6Gal-I expression was markedly upregulated in hepatocellular carcinoma (HCC) tissues and cells, high levels being associated with aggressive phenotype and poor prognosis. They examined the roles and mechanisms of ST6Gal-I in HCC tumorigenesis and metastasis in vitro and in vivo. [Oncogenesis] Full Article

3D Liver Membrane System by Co-Culturing Human Hepatocytes, Sinusoidal Endothelial and Stellate Cells

Scientists utilized a designed approach for the development of a 3D liver system. This approach made use of primary human sinusoidal endothelial cells, stellate cells and hepatocytes that were seeded sequentially on hollow fiber membranes in order to mimic the layers of cells found in vivo. [Biofabrication] Abstract

Report Lipopolysaccharide Induces the Differentiation of Hepatic Progenitor Cells into Myofibroblasts via Activation of the Hedgehog Signaling Pathway

Investigators found that hepatic progenitor cells (HPCs) promoted liver fibrosis in rats following carbon tetrachloride (CCl₄) treatment. The lipopolysaccharide (LPS) level in the portal vein was elevated and played a primary role in the fate of HPCs. In vitro, LPS inhibited the hepatobiliary differentiation of HPCs. [Cell Cycle] Abstract

Deletion of HNF1α in Hepatocytes Results in Fatty Liver-Related Hepatocellular Carcinoma in Mice

Researchers created hepatocyte-specific hepatocyte nuclear factor 1α (HNF1α) knockout mice using the Cre-loxP recombination system. The knockout mice displayed increased fatty acid synthesis in the liver. These mice spontaneously developed hepatocellular carcinoma through fatty liver without cirrhosis. [FEBS Lett] Abstract

5-ALA Ameliorates Hepatic Steatosis through AMPK Signaling Pathway

The authors fed C57BL/6J mice a high fat diet to induce a fatty liver disease and supplemented the diet-induced obese mice with 5-aminolevulinic acid (5-ALA). They found that 5-ALA activated AMPK signaling pathway, which were correlated with enhanced lipolysis and fatty acid β-oxidation. [J Mol Endocrinol] Abstract

MiR-30e Acts as a Tumor Suppressor in Hepatocellular Carcinoma Partly via JAK1/STAT3 Pathway

Scientists investigated the functional roles of miR-30e and their modulation of cancer networks in hepatocellular carcinoma (HCC) cells. MiR-30e mimicked significantly inhibited the proliferation, migration, and invasion of HepG2 and HuH7 cells, and promoted cell apoptosis, but did not influence the cell cycle. [Oncol Rep] Abstract

Physcion 8-O-β-Glucopyranoside Suppresses Tumor Growth of Hepatocellular Carcinoma by Downregulating PIM1

Researchers investigated the anti-tumor activity of physcion 8-O-β-glucopyranoside (PG) in hepatocellular carcinoma (HCC). Their results showed that PG significantly suppressed cell growth and induced apoptosis in vitro and in vivo. At molecular level, PG repressed the expression of Pim family kinases 1 (PIM1), which was responsible for the anti-tumor effect of PG in HCC. [Biomed Pharmacother] Abstract

Targeting Nuclear Receptors for the Treatment of Fatty Liver Disease

The authors summarize recent findings on the roles of nuclear receptors in fatty liver disease and discuss future perspectives to develop promising pharmacological strategies targeting nuclear receptors for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. [Pharmacol Ther] Abstract

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

New Preclinical Data on Can-Fite’s Namodenoson to be Presented

Can-Fite BioPharma Ltd. announced that Professor Rifaat Safadi M.D. will present new preclinical data on Can-Fite’s liver drug candidate namodenoson in a poster. [Press release from Can-Fite BioPharma Ltd. discussing research to be presented at the 1^st International Conference on Fatty Liver (ICFL), Seville] Press Release

FDA Grants Breakthrough Therapy Designation for Alnylam’s Givosiran for the Prophylaxis of Attacks in Patients with Acute Hepatic Porphyria

Alnylam Pharmaceuticals, Inc. announced that it has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 for the prophylaxis of attacks in patients with acute hepatic porphyria. [Alnylam Pharmaceuticals, Inc.] Press Release

Positive Outcome from the One-Year Pre-Planned Safety Review by the DSMB, in RESOLVE-IT Phase III Clinical Trial with Elafibranor

GENFIT announced that the Data Safety Monitoring Board (DSMB) issued a positive recommendation for the continuation of the RESOLVE-IT Phase III trial in nonalcoholic steatohepatitis without any modifications. [GENFIT] Press Release

Health Canada Grants Approval for Ocaliva™ (Obeticholic Acid) for the Treatment of Patients with Primary Biliary Cholangitis (PBC)

Intercept Pharmaceuticals, Inc. announced that Health Canada has granted a conditional approval for Ocaliva for the treatment of PBC, when used in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA. [Intercept Pharmaceuticals, Inc.] Press Release

Human Cell Atlas Data Platform Kicks Off with Support from CZI

The Chan Zuckerberg Initiative (CZI) has announced financial support for the Human Cell Atlas, which is using sequencing technology to redefine every cell in the body. Funding and engineering support from CZI will enable EMBL-EBI, the Broad Institute and the University of California Santa Cruz Genomics Institute to set up an open, cloud-based Data Coordination Platform to check, share and analyze the vast amounts of diverse information generated. [EMBL-EBI] Press Release

Trials of Embryonic Stem Cells to Launch in China

In the next few months, surgeons in the Chinese city of Zhengzhou will carefully drill through the skulls of people with Parkinson’s disease and inject four million immature neurons derived from human embryonic stem (ES) cells into their brains. Then they will patch the patients up, send them home and wait. This will mark the start of the first clinical trial in China using human ES cells, and the first one worldwide aimed at treating Parkinson’s disease using ES cells from fertilized embryos. [Nature News] Editorial

Pay-to-View Blacklist of Predatory Journals Set to Launch

Scholarly-services firm Cabell’s International says that it will launch its own list of predatory journals: those that deceive their authors or readers, for example by charging fees to publish papers without conducting peer review. [Nature News] Editorial

Web of Science Owner Buys up Booming Peer-Review Platform

The owner of the vast science-citation database Web of Science — Clarivate Analytics — is buying up a firm that has gathered hundreds of thousands of peer-review records, in a deal that could lead to new ways of organizing scientific peer review and preventing peer-review fraud. [Nature News] Editorial

NEW 3^rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 6-9, 2017
Mainz/Frankfurt, Germany

NEW Intestinal Organoid Virtual Training
October 17-25, 2017
None, None

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

NEW Research Fellow – Cancer Research (National University of Singapore)

Postdoctoral Studies – Liver Functions (Karolinska Instituet)

Postdoctoral Position – Novel Molecular and Cellular Mechanisms of Liver and Pancreatic Carcinogenesis (University of Illinois College of Medicine)

Assistant Professor – Renal and Hepatic Pharmacology (University of Manitoba)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

Postdoctoral Fellow – Obesity-Associated Complications (University of Kentucky College of Medicine)

Postdoctoral Position – Pediatrics/Cell Biology (Washington University School of Medicine)

Scientist – Hepatic Nuclear Receptor Biology (Moderna Therapeutics)

Research Lead – Liver Discovery (Spark Therapeutics)

Research Technician II – Translational Liver Cancer (Fred Hutchinson Cancer Research Center)

Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

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