Intestinal Cell News Volume 5.28 | Aug 2 2019

TOP STORY

LncRNA GLCC1 Promotes Colorectal Carcinogenesis and Glucose Metabolism by Stabilizing C-Myc

Investigators identified a long non-coding RNA, GLCC1, which was significantly upregulated under glucose starvation in colorectal cancer (CRC) cells, supporting cell survival and proliferation by enhancing glycolysis. Mechanistically, GLCC1 stabilized c-Myc transcriptional factor from ubiquitination by direct interaction with HSP90 chaperon and further specified the transcriptional modification pattern on c-Myc target genes, such as LDHA, consequently reprogrammed glycolytic metabolism for CRC proliferation. [Nat Commun] Full Article

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Activation of DR3 Signaling Causes Loss of ILC3s and Exacerbates Intestinal Inflammation

Researchers report that activation of death receptor 3 (DR3) signaling by an agonistic anti-DR3 antibody increased GM-CSF production from group 3 innate lymphoid cells (ILC3s) through the p38 MAPK pathway. GM-CSF caused accumulation of eosinophils, neutrophils and CD11b⁺CD11c⁺ myeloid cells, resulting in loss of ILC3s from the intestine in an IL-23-dependent manner and exacerbating colitis. [Nat Commun] Full Article

Nuclear KIT Induces a NFKBIB-RELA-KIT Autoregulatory Loop in Imatinib-Resistant Gastrointestinal Stromal Tumors

The authors identified the binding of nuclear KIT to the promoter of NFKB inhibitor beta (NFKBIB) by chromatin immunoprecipitation (ChIP) sequencing and ChIP assays, which was accompanied with enhanced NFKBIB protein expression in gastrointestinal stromal tumors (GIST) cells. Clinically, high NCCN risk GISTs had significantly higher mean expression levels of nuclear phospho-KIT and NFKBIB as compared with those of intermediate or low/very low-risk GISTs. [Oncogene] Full Article

Long Noncoding RNA LINC02418 Regulates MELK Expression by Acting as a ceRNA and May Serve as a Diagnostic Marker for Colorectal Cancer

Scientists evaluated the effect of LINC02418 on colorectal cancer tumorigenesis and its regulatory functions of absorbing microRNA and indirectly stimulating protein expression by acting as a ceRNA. Mechanistically, LINC02418 acted as a ceRNA to upregulate MELK expression by absorbing miR-1273g-3p. [Cell Death Dis] Full Article

Cep131 Overexpression Promotes Centrosome Amplification and Colon Cancer Progression by Regulating Plk4 Stability

Researchers demonstrated that Cep131 physically interacted with Plk4 following phosphorylation of residues S21 and T205. Localizing at the centriole, phosphorylated Cep131 had an increased capability to interact with STIL, leading to further activation and stabilization of Plk4 for initiating centrosome duplication. [Cell Death Dis] Full Article

Imbalance of Autophagy and Apoptosis in Intestinal Epithelium Lacking the Vitamin D Receptor

Investigators used in vivo vitamin D receptor (VDR)^lox and VDR^∆IEC mice and ex vivo organoids generated from small intestine and colon tissues. They found that VDR deficiency induced more apoptotic cells and significantly increased cell death in the small intestine and colon of VDR^∆IEC mice. [FASEB J] Abstract

Increased Glucocorticoid Receptor Activity and Proliferation in Metastatic Colon Cancer

Scientists used proliferation/invasion assays, western blot, RT-qPCR, immunofluorescence staining and quantitative methylation to study glucocorticoid-GR signaling, including the involvement of CDK1, in human colon adenocarcinoma cell lines HT29 and T84. Nuclear expression levels of GR were significantly upregulated in metastatic T84 cells, and glucocorticoid derivative, dexamethasone treatment caused increased proliferation and invasion in T84 cell, compared to HT29 cell. [Sci Rep] Full Article

Ru(II)-Thymine Complex Causes DNA Damage and Apoptotic Cell Death in Human Colon Carcinoma HCT116 Cells Mediated by JNK/p38/ERK1/2 via a p53-Independent Signaling

The Ru(II)-thymine complex increased significantly the percentage of apoptotic HCT116 cells. Co-treatment with a JNK/SAPK inhibitor, p38 MAPK inhibitor and MEK inhibitor, which inhibited the activation of ERK1/2, caused a marked reduction of the percentage of complex-induced apoptotic cells. [Sci Rep] Full Article

Three-Dimensional Analysis of Single Molecule FISH in Human Colon Organoids

The authors developed a three-day protocol and validation method to perform single-molecule RNA fluorescence in situ hybridizationsm (FISH) in 3D in whole human organoids. They provided a number of applications to exemplify the diverse possibilities for the simultaneous detection of distinct mRNA transcripts, evaluation of their spatial distribution and the identification of divergent cell lineages in 3D in organoids. [Biol Open] Abstract | Full Article

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Intestinal Epithelial Barrier Functions in Aging

The intestinal epithelial barrier protects the mucosa of the gastrointestinal-tract and plays a key role in maintaining the host homeostasis. It encompasses several elements that include the intestinal epithelium and biochemical and immunological products, such as the mucus layer, antimicrobial peptides (AMPs) and secretory immunologlobulin A. [Ageing Res Rev] Abstract

Exploring the Best Treatment Options for BRAF-Mutant Metastatic Colon Cancer

The BRAF^V600E mutation is a well-accepted poor prognostic factor in patients with metastatic colorectal cancer, as it confers Ras-independent stimulation of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway involved in proliferation, migration, angiogenesis and the suppression of apoptosis. [Br J Cancer] Abstract

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

Italfarmaco Enters Binding Term Sheet Agreement with Neupharma for an Exclusive Option to Develop and Commercialize Inhaled Teicoplanin

Italfarmaco Group announced that Italfarmaco SpA has entered into a binding term sheet agreement with Neupharma for an exclusive option to develop and commercialize inhaled teicoplanin. Intravenously administered teicoplanin remains one of the most efficacious antibiotics used to treat cystic fibrosis patients with Methicillin-Resistant Staphylococcus Aureus. [Italfarmaco Group] Press Release

Axonics^® Announces One-Year Top-Line Clinical Results from Its ARTISAN-SNM Pivotal Study

Axonics Modulation Technologies, Inc. announced completion of one-year follow-ups and top-line clinical results from its ARTISAN-SNM pivotal clinical study conducted under an FDA Investigational Device Exemption designed to evaluate the safety and efficacy of the Axonics r-SNM^® System. [Axonics Modulation Technologies, Inc.] Press Release

Janssen Receives CHMP Positive Opinion for Stelara^® (Ustekinumab) Recommending Approval for the Treatment of Moderately to Severely Active Ulcerative Colitis in the EU

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion recommending marketing authorization in the European Union (EU) for the use of ustekinumab for the treatment of adult patients with moderately to severely active ulcerative colitis, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic or have medical contraindications to such therapies. [The Janssen Pharmaceutical Companies of Johnson & Johnson] Press Release

Algernon Pharmaceuticals Announces Emoxypine (NP-178), a Top Selling Drug in Russia, as Its Lead Drug for Inflammatory Bowel Disease

Algernon Pharmaceuticals Inc. reported that its lead drug for inflammatory bowel disease is Emoxypine, an orally delivered small molecule. The drug is currently one of the top five selling drugs on the essential medicines list in Russia for the treatment of several neurological conditions. [Algernon Pharmaceuticals (GlobeNewsire, Inc.)] Press Release

Dr. Jason Spence shares his insights on the derivation of organoids from hPSCs. Listen Now

‘Tropical Trump’ Sparks Unprecedented Crisis for Brazilian Science

Since Bolsonaro took office in January, Brazil’s researchers have faced funding cuts and repeated attempts by the administration to roll back protections for the environment and Indigenous populations. [Nature News] Editorial

‘No One Is Immune’: Alaska’s Scientists Despair over Plan to Shrink State Universities

The University of Alaska’s governing board plans to consolidate campuses to cope with a 40% cut in state funding. [Nature News] Editorial

China’s Scientists Alarmed, Bewildered by Growing Anti-Chinese Sentiment in the United States

Scientists in China are concerned about what they see as growing anti-Chinese sentiment in the United States. They dismiss claims of a vast conspiracy to steal US intellectual property and worry that new visa restrictions, scrutiny of export of scientific devices, and US investigations of Chinese and Chinese American scientists will hinder international collaborations. That could harm both countries’ research efforts as well as global scientific progress, many say. [ScienceInsider] Editorial

NEW European Cancer (ECCO) Summit 2019
September 12-14, 2019
Brussels, Belgium

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

NEW Postdoctoral Fellow – Designer Probiotics (Massacheusetts General Hospital)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Multi-Omics in Intra-Tumor Heteregenity (The Institute of Cancer Research)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Postdoctoral Researcher – Microbiome Interactions in IBD (Quadram Institute Bioscience)

Postdoctoral Fellowship – Cancer Biology (Ninewells Hospital and Medical School)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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