Pancreatic Cell News Volume 9.28 | Jul 17 2018

TOP STORY

The BRG1/SOX9 Axis Is Critical for Acinar Cell-Derived Pancreatic Tumorigenesis

Brahma related gene 1 (BRG1) bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. SOX9 expression was downregulated in BRG1-depleted acinar-to-ductal metaplasia/pancreatic intraepithelial neoplasias. [J Clin Invest] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Discovery of a Drug Candidate for GLIS3-Associated Diabetes

Researchers developed a “minimal component” protocol to generate late-stage pancreatic progenitors (PP2) that differentiate to mono-hormonal glucose-responding β-like (PP2-β) cells. They discovered that GLIS3^−/− hESCs showed impaired differentiation, with significant death of PP2 and PP2-β cells, without impacting the total endocrine pool. [Nat Commun] Full Article

Identification of a Panel of miRNAs as Positive Regulators of Insulin Release in Pancreatic Β-Cells

Experiments in MIN6 cells illustrated that miR-15a, miR-424, miR-497, and miR-185 positively regulated insulin biosynthesis by co-inhibiting uncoupling protein 2 (UCP2) expression. Furthermore, the four miRNAs were found to post-transcriptionally repress UCP2 expression by directly targeting the 3’UTR of UCP2 mRNA. [Cell Physiol Biochem] Full Article

Gli2 Mediated Activation of Hedgehog Signaling Attenuates Acute Pancreatitis via Balancing Inflammatory Cytokines in Mice

Gli2 upregulation changed the cytokine expression profile in mouse pancreatic acinar cells, mainly by decreasing the pro-inflammatory cytokines interleukin (IL)-6, interferon-γ, and FasL. The anti-inflammatory cytokine IL-10 was upregulated by Gli2 overexpression. Interdiction of Gli2 by the Gli-specific inhibitor GANT61 exacerbated acute pancreatitis in mice and altered the balance of inflammatory cytokines. [Cell Physiol Biochem] Full Article

Opposing Effects of Intracellular vs. Extracellular Adenine Nucleotides on Autophagy: Implications for β-Cell Function

Scientists found that in β-cells the AMPK activator 5-amino-4-imidazolecarboxamide ribofuranoside (AICAR) inhibited, rather than stimulated, autophagy. Adenosine regulated autophagy in a concentration-dependent manner: at high concentrations, it mimicked the AICAR effect on autophagy, whereas at low concentrations it stimulated autophagy through its cognate A1 receptor. [J Cell Sci] Abstract

Gene Signature of Proliferating Human Pancreatic α-Cells

Researchers identified two large subpopulations and a smaller cluster of proliferating α-cells with increased expression of genes involved in cell cycle regulation. The proliferating α-cells were differentiated, had normal levels of GCG expression and showed no signs of cellular stress. [Endocrinology] Abstract

PANCREATIC CANCER

Silencing of MUC20 Suppresses the Malignant Character of Pancreatic Ductal Adenocarcinoma Cells through Inhibition of the HGF/MET Pathway

Mucin 20 (MUC20) knockdown with siRNA decreased cell viability, as well as migration and invasion induced by pancreatic stellate cells in HPAC and HPAF-II cells. The authors indicated that MUC20 knockdown decreased HGF-mediated phosphorylation of MET in pancreatic ductal adenocarcinoma cells. [Oncogene] Full Article

LncRNA PVT1 Triggers Cyto-Protective Autophagy and Promotes Pancreatic Ductal Adenocarcinoma Development via the miR-20a-5p/ULK1 Axis

Investigators found that plasmacytoma variant translocation 1 (PVT1) levels paralleled those of ULK1 protein in pancreatic ductal adenocarcinoma (PDA) cancer tissues. PVT1 promoted cyto-protective autophagy and cell growth by targeting ULK1 both in vitro and in vivo. PVT1 acted as a sponge to regulate miR-20a-5p and thus affected ULK1 expression and the development of PDA. [Mol Cancer] Full Article

S100A10, a Novel Biomarker in Pancreatic Ductal Adenocarcinoma

Scientists introduce the plasminogen receptor S100A10 as a novel predictive biomarker and a driver of pancreatic tumor growth and invasion. S100A10 expression was driven by promoter methylation and the oncogene KRAS. S100A10 knockdown reduced surface plasminogen activation, invasiveness and in vivo growth of pancreatic cancer cell lines. [Mol Oncol] Abstract | Full Article

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Epigenetic Regulation of Toll-Like Receptors and Its Roles in Type 1 Diabetes

Epigenetics has recently been proven to be a new regulator of toll-like receptor (TLR) expression. The authors focus on these epigenetic mechanisms of regulation of TLRs and the role of TLRs in the pathogenesis of type 1 diabetes. [J Mol Med (Berl)] Abstract

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

Diabetes Research Institute Launches New Clinical Trial to Explore Effects of Omega-3 Fatty Acids and Vitamin D in Type 1 Diabetes

Scientists from the Diabetes Research Institute at the University of Miami Miller School of Medicine announced the launch of a new clinical trial that will assess the impact of high-dose omega-3 fatty acids and vitamin D supplementation on halting the progression of type 1 diabetes. [Diabetes Research Institute Foundation] Press Release

U.S. FDA Extends Review Timeline for INVOKANA^® (Canagliflozin) Supplemental New Drug Application

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the FDA has extended the review timeline for a supplemental New Drug Application (sNDA) for INVOKANA^®. The sNDA seeks a new indication for INVOKANA^® to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular (CV) disease or are at risk for CV disease. [Janssen Global Services, LLC] Press Release

Women Maintain NIH Funding Similar to Men: Study

Female principal investigators apply for fewer grants, but retain support once they get it. Of nearly 35,000 researchers who received funding from the National Institutes of Health (NIH) between 1991 and 2010, men and women maintain funding at roughly the same rates. [The Scientist] Editorial

Science Journals End Open-Access Trial with Gates Foundation

The publisher of Science ended a pilot partnership that allowed open-access (OA) publishing for researchers funded by the Bill & Melinda Gates Foundation. The trial was an effort to accommodate a policy clash between the Gates Foundation, which has enforced strict OA demands since 2017, and publishers that run subscription journals which don’t comply with those terms. [Nature News] Editorial

Researchers Celebrate Rejection of Controversial Copyright Policy

Early-career researchers are pleased at European leaders’ rejection of a copyright policy that would have introduced restrictions to text-and-data mining of scientific papers. [Chemistry World] Editorial

NEW 11^th American Association for Cancer Research (AACR) and Japanese Cancer Association (JCA) Joint Conference
February 8-12, 2019
Maui, Hawaii, United States

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

NEW Postdoctoral Positions – Pancretic Cancer Research (The University of Texas MD Anderson Cancer Center)

NEW Postdoctoral Research Fellow – Metabolism, Diabetes & Obesity Research (The University of Edinburg)

Research Assistant – Therapeutic Target in Pancreatic Cancer (King’s College London)

Postdoctoral Scholars – Molecular & Cellular Biology in Diabetes & Metabolism (University of Oklahoma)

Lecturer/ Professor/ Clinical Academic – Diabetes (University of Exeter)

Postdoctoral Research Fellow – Drivers of Pancreatic Cancer Metastasis (The Moffitt Cancer Center)

Postdoctoral Associate – Type 1 Diabetes Research (University of Florida)

Assistant or Associate Professor (Tenure Track) – Immunopathology of Metabolic Diseases)

EBPOD Fellowship – Pancreatic Cancer Analysis (European Molecular Biology Laboratory)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

Doctoral Thesis Position – Diabetes Research (Universite Libre de Bruxelles)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral Fellow – Epigenetic Regulation of Pancreatic Beta-Cell Mass (City of Hope)

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