Intestinal Cell News Volume 5.04 | Feb 8 2019

TOP STORY

The p300/YY1/miR-500a-5p/HDAC2 Signaling Axis Regulates Cell Proliferation in Human Colorectal Cancer

Mechanistically, miR-500a-5p directly targeted HDAC2 and inhibited HDAC2-mediated proliferation in colorectal cancer in nude mice. Furthermore, YY1 bound to the promoter of miR-500a-5p and negatively regulated its transcription. Restoration of miR-500a-5p expression was up-regulated via the p300/YY1/HDAC2 complex. [Nat Commun] Full Article

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Circular RNA circNRIP1 Acts as a MicroRNA-149-5p Sponge to Promote Gastric Cancer Progression via the AKT1/mTOR Pathway

Scientists discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in gastric cancer (GC) cells. miR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviors of circNRIP1. [Mol Cancer] Full Article

3,3′-Diindolylmethane Inhibits Patient-Derived Xenograft Colon Tumor Growth by Targeting COX1/2 and ERK1/2

To identify possible molecular targets of 3,3’-diindolymethane (DIM), 11 potential candidate proteins were validated by an in vitro kinase or enzyme assay. The inhibition of cell growth by DIM was dependent on the expression of COX1/2 or ERK1/2 proteins. Notably, oral administration of DIM suppressed patient-derived xenograft colon tumor growth in an in vivo mouse model. [Cancer Lett] Abstract

Met Inhibition Revokes IFNγ-Induction of PD-1 Ligands in MET-Amplified Tumors

Programmed cell death ligand 1 (PD-L1) /PD-L2 expression and signaling pathways downstream of MET or interferon-γ (IFNγ) were analyzed in MET-amplified tumor cell lines and in patient-derived tumor organoids, in basal condition, upon IFNγ stimulation, and after anti-MET therapy. [Br J Cancer] Full Article

Cytoplasmic Asporin Promotes Cell Migration by Regulating TGF-β/Smad2/3 Pathway and Indicates a Poor Prognosis in Colorectal Cancer

Asporin (ASPN) could promote proliferation, migration, and invasion of colorectal cancer cells, and inhibited apoptosis by activating Akt/Erk and TGF-β/Smad2/3 signaling. Further investigations revealed that ASPN interacted with Smad2/3, facilitated its translocation into the nucleus, and up-regulated the expression of epithelial-mesenchymal transition related genes. [Cell Death Dis] Full Article

Msx1 Loss Suppresses Formation of the Ectopic Crypts Developed in the Apc-Deficient Small Intestinal Epithelium

Ablation of the msh homeobox 1 (Msx1) gene led to the disappearance of ectopic crypts and loss of differentiated cells. Moreover, tumors arising from Msx1-deficient cells displayed altered morphology reminiscent of villous adenomas. In human tumor specimens, MSX1 displayed significantly increased expression in colonic neoplasia with a descending tendency during the lesion progression towards colorectal carcinoma. [Sci Rep] Full Article

FOXM1 Modulates 5-FU Resistance in Colorectal Cancer through Regulating TYMS Expression

A synergistic effect was observed following treatment of colorectal cancer (CRC) cells with an inhibitor of FOXM1, thiostrepton, in combination with 5-fluoruracil (5-FU). The combination treatment decreased colony formation and migration, and induced cell cycle arrest, DNA damage, and apoptosis in CRC cell lines. [Sci Rep] Full Article

IFN/STAT Signaling Controls Tumorigenesis and the Drug Response in Colorectal Cancer

Researchers established 42 organoids from three classical familial adenomatous polyposis coli (FAP) patients and two attenuated FAP patients. Comprehensive gene expression analysis demonstrated a close association between IFN/STAT signaling and the phenotypic features of FAP patients. [Cancer Sci] Abstract

Characterization of Exopolysaccharides Produced by Microalgae with Antitumor Activity on Human Colon Cancer Cells

Monosaccharide analysis indicated that the exopolysaccharides consisted of ten different kinds of sugars and derivatives, respectively. The results showed that they had significant antitumor effects considering the inhibitory effects on cell viabilities, and could decrease colony amounts at the tested dosage. [Int J Biol Macromol] Abstract

Erlotinib Inhibits Colon Cancer Metastasis through Inactivation of TrkB-Dependent ERK Signaling Pathway

Human colon adenocarcinoma cell lines pretreated with exogenous C-X-C motif chemokine ligand 8 were used to assess the suppressive effect of erlotinib on tumor metastasis, including anoikis, epithelial-mesenchymal transformation, migration, and invasion. [J Cell Biochem] Abstract

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Defective Proteostasis in Celiac Disease as a New Therapeutic Target

Recent evidence indicates that CF transmembrane conductance regulator (CFTR) is inhibited by a gluten/gliadin-derived peptide, causing an acquired state of CFTR inhibition within the gut that contributes to the pathogenesis of celiac disease. [Cell Death Dis] Full Article

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Arena Pharmaceuticals Presents Preclinical and Early Clinical Development Data for Olorinab

Arena Pharmaceuticals, Inc. presented preclinical and early clinical development data from its investigative drug candidate olorinab, a peripherally restricted, highly selective, full agonist of the cannabinoid receptor type 2 in development for the treatment of visceral pain associated with gastrointestinal diseases. [Press release from Arena Pharmaceuticals, Inc. discussing research presented at the Crohn’s & Colitis Congress^®, Las Vegas] Press Release

Learn the basics of culturing mouse intestinal organoids with an instructional video series. Watch the Video Now

Pharm-Olam Enrolls Patients in Zealand Pharma Orphan Drug Study

Pharm-Olam is now enrolling patients in the US and Europe into a pivotal Phase III study within the treatment of short bowel syndrome. Initiated in early October 2018, the study is a placebo-controlled, randomized, parallel-group, double-blind clinical trial with fixed-dose injections. [Pharm-Olam International] Press Release

Foundation Awards over $2 Million for Collaborative IBD Research Projects

The Kenneth Rainin Foundation announced that it has awarded over $2 million in grants through its Synergy Awards program. This program encourages collaboration among researchers from different disciplines to advance the study of IBD. The Foundation also announced it will accept Letters of Inquiry for its Innovator Awards program from February 4 through March 15, 2019. [Kenneth Rainin Foundation] Press Release

Fluidigm Announces Participation in Life Science/Pharma and Academic Consortium to Study T Cell-Driven Immune-Mediated Inflammatory Diseases

Fluidigm Corporation announced it is one of 11 partners in the TIMID Consortium, a unique effort of six academic institutions and five life science and pharma companies that utilizes both mass cytometry and Imaging Mass Cytometry^™ along with other technologies to explore the common cellular basis of T cell-driven immune-mediated inflammatory diseases. [Fluidigm Corporation (GlobeNewswire, Inc.)] Press Release

Most Biomedical Studies Fail to Report If Results Differ by Sex

Nearly three-quarters of biomedical studies fail to report whether outcomes differ for men and women, according to a study which raises concerns about gender bias. Analysis of more than 11.5m medical research papers published between 1980 and 2016 found a majority overlooked the role of sex differences in genetics, physiology and the way the body responds to drugs. [The Guardian] Editorial

NIH Asks Inspector General to Investigate 12 Allegations of Foreign Influence in US Research

The National Institutes of Health (NIH) has referred 12 allegations relating to foreign influence over US-funded research to a federal oversight office, Sen. Chuck Grassley said. Grassley, the chairman of the Senate Finance Committee, has repeatedly demanded information from the NIH after the agency revealed in August it was investigating a half-dozen academic institutions — specifically, researchers who may have failed to disclose financial ties to foreign governments. [STAT News] Editorial

NEW DASCS2019 Stem Cell Conference
May 2-3, 2019
Vejle, Denmark

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NEW Advanced Research Assistant – Inflammatory Bowel Disease Research (Wellcome Sanger Institute)

Research Associate – Infections, Inflammation & Colorectal Cancer (Imperial College of London)

PhD Student – Biopharmaceutical Drug Delivery (Technical University of Denmark)

Research Assistant – Stem Cell Biology of the Intestine (Cancer Research UK Cambridge Institute)

Postdoctoral Position – Colon Cancer (Vanderbilt University)

Postdoctoral Research Opportunities – Cancer Center Program (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Fellow – Intestinal Immune System (Washington University School of Medicine, St.Louis)

Research Scientist – Intestinal Biology (Evotec AG)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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