Hepatic Cell News Volume 1.08 | Mar 17 2017

TOP STORY

Hepatic IFIT3 Predicts Interferon-α Therapeutic Response in Patients of Hepatocellular Carcinoma

As the induced interferon-αIFN-stimulated genes (ISGs) expression following IFN-α treatment plays pivotal roles in IFN-α effects, scientists screened ISGs expression in hepatocellular carcinoma (HCC) tissues and found several ISGs were significantly decreased in HCC. Interestingly, expressions of IFN-induced proteins with tetratricopeptide repeats (IFIT) family members, including IFIT1, IFIT2, IFIT3, and IFIT5, were all decreased in HCC tissues. [Hepatology] Abstract

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Inhibition of Hepatic Lipogenesis Enhances Liver Tumorigenesis by Increasing Antioxidant Defense and Promoting Cell Survival

Blocking lipogenesis in cultured liver cancer cells is sufficient to decrease cell viability; however, it is not known whether blocking lipogenesis in vivo can prevent liver tumorigenesis. The authors inhibited hepatic lipogenesis in mice by liver-specific knockout of acetyl-CoA carboxylase genes and treated the mice with the hepatocellular carcinogen diethylnitrosamine. Mice lacking hepatic lipogenesis have a twofold increase in tumor incidence and multiplicity compared to controls. [Nat Commun] Full Article

MTA1 Modulated by miR-30e Contributes to Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma through an ErbB2-Dependent Pathway

Researchers investigated MTA1’s upstream regulation and downstream effector in human hepatocellular carcinoma (HCC). In total, 94 paired HCC and adjacent tissue samples were involved in the study, and the results indicated that decreased miR-30e levels were associated with increased MTA1 levels in human HCC. [Oncogene] Abstract

Loss of Exosomal miR-320a from Cancer-Associated Fibroblasts Contributes to HCC Proliferation and Metastasis

The authors performed microRNA (miRNA) sequencing of exosomes derived from cancer-associated fibroblasts (CAFs) and corresponding para-cancer fibroblasts of hepatocellular carcinoma (HCC) patients. They found a significant reduction in the miR-320a level in CAF-derived exosomes. Using exogenous miRNAs, they demonstrated that stromal cells could transfer miRNA to HCC cells. In vitro and in vivo studies further revealed that miR-320a could function as an antitumor miRNA by binding to its direct downstream target PBX3 to suppress HCC cell proliferation, migration and metastasis. [Cancer Lett] Abstract

Bidirectional Transcription of Linc00441 and RB1 via H3K27 Modification-Dependent Way Promotes Hepatocellular Carcinoma

Investigators focused on the bidirectional transcripted long noncoding RNA (Linc00441) with neighbor gene retinoblastoma gene (RB1) to investigate whether Linc00441 is involved in the suppression of RB1 in hepatocellular carcinoma (HCC). They found that aberrant upregulated intranuclear Linc00441 was reversely correlated with RB1 expression in human HCC samples. [Cell Death Dis] Full Article

Antifibrotic Effect of Pirfenidone in a Mouse Model of Human Nonalcoholic Steatohepatitis

Researchers employed melanocortin 4 receptor-deficient (MC4R-KO) mice as a mouse model with human non-alcoholic steatohepatitis (NASH)-like phenotypes to elucidate the effect and action mechanisms of pirfenidone (PFD) on the development of NASH. PFD markedly attenuated liver fibrosis in western diet (WD)-fed MC4R-KO mice without affecting metabolic profiles or steatosis. PFD prevented liver injury and fibrosis associated with decreased apoptosis of liver cells in WD-fed MC4R-KO mice. [Sci Rep] Full Article

Generation of Non-Viral, Transgene-Free Hepatocyte Like Cells with PiggyBac Transposon

The authors attempted to utilize the piggyBac transposon system to generate induced hepatocyte-like cells (iHeps) by integrating a transgene consisting of Hnf4a and Foxa3, and successfully obtained functional iHeps. They then demonstrated removal of the transgene to obtain transgene-free iHeps, which still maintained hepatocyte functions. [Sci Rep] Full Article

Applying Stable Isotope Labeled Amino Acids in Micropatterned Hepatocyte Co-Culture to Directly Determine the Degradation Rate Constant for CYP3A4

In the current investigation, stable isotope labeled amino acids in culture was applied to a long-lived primary human hepatocyte culture, HepatoPac, to directly monitor the degradation of CYP3A4. This approach allowed selective isotope labeling of a population of de novo synthesized CYP3A4, and specific quantification of proteins with mass spectrometry to determine the CYP3A4 degradation within the hepatocytes. [Drug Metab Dispos] Abstract | Full Article

Hepatitis C-Related Hepatocellular Carcinoma in the Era of New Generation Antivirals

The authors discuss how a molecular signature in the liver has been associated with cancer risk even after viral cure. Direct-acting antivirals may affect cancer development and recurrence, which needs to be determined in further investigation. [BMC Med] Full Article

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

AbbVie Granted Priority Review in Japan for Its Investigational Regimen of Glecaprevir/Pibrentasvir (G/P) for the Treatment of All Major Genotypes of Chronic Hepatitis C

AbbVie announced that priority review has been granted by the Japanese Ministry of Health, Labor and Welfare for its investigational, pan-genotypic, ribavirin-free regimen of G/P for the treatment of all major genotypes of the chronic hepatitis C virus. [AbbVie] Press Release

twoXAR Announces Preclinical Proof-of-Concept Data on Novel Liver Cancer Candidate

twoXAR, Inc. announced that its candidate targeting hepatocellular carcinoma (HCC), TXR-311, has shown positive results in cell-based assays. TXR-311 is a molecule that twoXAR identified as having a high probability of being effective in treating HCC. [twoXAR, Inc.] Press Release

United Kingdom Moves Forward with Controversial Embryo Technique

Making heritable genetic changes to eggs and sperm was prohibited in the United Kingdom until Parliament approved a new law allowing the technique in 2015. In December 2016, the Human Fertilization and Embryo Authority announced that it would be willing to grant a license to use the technique in patients. The Telegraph reported that the agency has granted its first license to Newcastle University, where researchers have been working on lab-based experiments for years. [ScienceInsider] Editorial

Pasteur Institute’s Scientists Make Last-Ditch Plea to Keep Their President

Following a string of failed attempts to keep their president Christian Bréchot on after he reaches the mandated retirement age, leading researchers have continued to agitate quietly in his favor — even though the institute’s board of directors has made what seems to be a final decision on the matter and is starting a search for Bréchot’s successor. [Nature News] Editorial

NEW World Advanced Therapies & Regenerative Medicine Congress 2017
May 17-19, 2017
London, United Kingdom

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

NEW Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University)

NEW Non-Tenure Track Professor – Regenerative Medicine (University of Hong Kong – Karolinska Institute Collaboration)

NEW PhD-Candidate – Non-Alcoholic Steatohepatitis (Maastricht University)

Postdoctoral Fellowship – Metabolism (University of San Francisco)

Research Fellow – Hepatocytes (National University of Singapore)

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

Associate or Full Professor – Gastroenterology (University of Washington)

Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

Senior Scientist – Oncology (Genentech Research)

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