Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our aim was to conduct a pilot case-control study of RNA expression profile using RNA sequencing of rectosigmoid mucosa of nine females with -diarrhea-predominant irritable bowel syndrome (IBS-D) with accelerated colonic transit and nine female healthy controls. Mucosal total RNA was isolated and purified, and next-generation pair-end sequencing was performed using Illumina TruSeq. Analysis was carried out using a targeted approach toward 12 genes previously associated with IBS and a hypothesis-generating approach. Of the 12 targeted genes tested, patients with IBS-D had decreased mRNA expression of TNFSF15 (fold change controls to IBS-D: 1.53, P = 0.01). Overall, up- and downregulated mRNA expressions of 21 genes (P = 10(-5) to 10(-8); P values with false detection rates are shown) were potentially relevant to IBS-D including the following: neurotransmitters [P2RY4 (P = 0.001), vasoactive intestinal peptide (VIP, P = 0.02)]; cytokines [CCL20 (P = 0.019)]; immune function [C4BPA complement cascade (P = 0.0187)]; interferon-related [IFIT3 (P = 0.016)]; mucosal repair and cell adhesion [trefoil protein (TFF1, P = 0.012)], retinol binding protein [RBP2 (P = 0.017)]; fibronectin (FN1, P = 0.009); and ion channel functions [guanylate cyclase (GUCA2B, P = 0.017), PDZ domain-containing protein 3 (PDZD3, P = 0.029)]. Ten genes associated with functions related to pathobiology of IBS-D were validated by RT-PCR. There was significant correlation in fold changes of the selected genes (Rs = 0.73, P = 0.013). Up- or downregulation of P2RY4, GUC2AB, RBP2, FNI, and C4BPA genes were confirmed on RT-PCR, which also revealed upregulation of farnesoid X receptor (FXR) and apical sodium-coupled bile acid transporter (IBAT/ASBT). RNA-Seq and RT-PCR analysis of rectosigmoid mucosa in IBS-D show transcriptome changes that provide the rationale for validation studies to explore the role of mucosal factors in the pathobiology of IBS-D.
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PMID:RNA sequencing shows transcriptomic changes in rectosigmoid mucosa in patients with irritable bowel syndrome-diarrhea: a pilot case-control study. 2621 40

Pancreatic cancer has an extremely high mortality rate due to its aggressive metastatic nature. Resolving the underlying mechanisms will be crucial for treatment. Here, we found that overexpression of IL-17B receptor (IL-17RB) strongly correlated with postoperative metastasis and inversely correlated with progression-free survival in pancreatic cancer patients. Consistently, results from ex vivo experiments further validated that IL-17RB and its ligand, IL-17B, plays an essential role in pancreatic cancer metastasis and malignancy. Signals from IL-17B-IL-17RB activated CCL20/CXCL1/IL-8/TFF1 chemokine expressions via the ERK1/2 pathway to promote cancer cell invasion, macrophage and endothelial cell recruitment at primary sites, and cancer cell survival at distant organs. Treatment with a newly derived monoclonal antibody against IL-17RB blocked tumor metastasis and promoted survival in a mouse xenograft model. These findings not only illustrate a key mechanism underlying the highly aggressive characteristics of pancreatic cancer but also provide a practical approach to tackle this disease.
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PMID:Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines. 2575 18