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MicroRNAs and extracellular vesicles in cholangiopathies
Authors:P Olaizola  PY Lee-Law  A Arbelaiz  A Lapitz  MJ Perugorria  L Bujanda  JM Banales
Institution:1. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain;2. National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Spain;3. Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, Netherlands;4. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
Abstract:Cholangiopathies encompass a heterogeneous group of disorders affecting biliary epithelial cells (i.e. cholangiocytes). Early diagnosis, prognosis and treatment still remain clinically challenging for most of these diseases and are critical for adequate patient care. In the past decade, extensive research has emphasized microRNAs (miRs) as potential non-invasive biomarkers and tools to accurately identify, predict and treat cholangiopathies. MiRs can be released extracellularly conjugated with lipoproteins or encapsulated in extracellular vesicles (EVs). Research on EVs is also gaining attention since they are present in multiple biological fluids and may represent a relevant source of novel non-invasive biomarkers and be vehicles for new therapeutic approaches. This review highlights the most promising candidate miRs and EV-related biomarkers in cholangiopathies, as well as their relevant roles in biliary pathophysiology. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Research strategy

PubMed search (April 2017) was done with the following terms: “microRNA”, “miRNA”, “miR”, “extracellular vesicles”, “EV”, “exosomes”, “primary biliary cholangitis”, “primary biliary cholangitis”, “PBC”, “primary sclerosing cholangitis”, “PSC”, “cholangiocarcinoma”, “CCA”, “biliary atresia”, “BA”, “polycystic liver diseases”, “PLD”, “cholangiopathies”, “cholestatic liver disease”. Most significant articles in full-text English were selected. The reference lists of selected papers were also considered.
Keywords:15-PGDH  15-hydroxyprostaglandin dehydrogenase  ADPKD  autosomal dominant polycystic kidney disease  ADPLD  autosomal dominant polycystic liver disease  AE2/SLC4A2  ?  ALP  alkaline phosphatase  AMA  anti-mitochondrial antibody  ARPKD  autosomal recessive polycystic kidney disease  Ars2  arsenic resistance protein 2  ASGPR1  asialoglycoprotein receptor 1  AUC  area under the curve  BA  biliary atresia  CA19-9  cancer antigen 19-9  CCA  cholangiocarcinoma  CCL2  C-C motif chemokine ligand 2  Cdc25A  cell division cycle 25A  CDH6  cadherin-6  CDK6  cyclin-dependent kinase 6  CHEK2  checkpoint kinase 2  c-Myc  myc proto-oncogene protein  CXCL1  chemokine (C-X-C motif) ligand 1  eCCA  extrahepatic cholangiocarcinoma  EGFR  epidermal growth factor receptor  ELK1  ETS domain-containing protein Elk-1  EMT  epithelial mesenchymal transition  ERK  extracellular signal-regulated kinases  EV  extracellular vesicle  FDA  food and drug administration  FIBG  fibrinogen gamma chain  FOXA1  forkhead box protein A1  FOXO1  forkhead box protein O1  FXR  farnesoid X receptor  GSK3β  glycogen synthase kinase-3 beta  HCC  hepatocellular carcinoma  HDAC4  histone deacetylase 4  HSC  hepatic stellate cell  iCCA  intrahepatic cholangiocarcinoma  IGF1R  insulin-like growth factor-1 receptor  IL  interleukin  IL1β  interleukin-1 beta  InsP3R3  type III inositol 1  4  5-triphosphate receptor  ITGB4  integrin beta-4  MAPK  mitogen activated protein kinase  MAP3K8  mitogen-activated protein kinase kinase kinase 8  MBD2  methyl-CpG-binding domain protein 2  Mcl-1  induced myeloid leukemia cell differentiation protein Mcl-1  MDR1  multidrug resistant protein 1  miR  microRNA  MMP  matrix metalloproteinase  MSC  mesenchymal stem cell  mTOR  mechanistic target of rapamycin  MVB  multivesicular body  NCAM1  neural cell adhesion molecule 1  NDRG2  N-myc downstream-regulated gene 2  NUAK1  (nua) family kinase 1  PBMC  peripheral blood mononuclear cells  PBC  primary biliary cholangitis  pCCA  perihilar cholangiocarcinoma  PDC-E2  pyruvate dehydrogenase complex-E2  PDCD4  programmed cell death protein 4  Per1  period circadian protein homolog 1  PLD  polycystic liver disease  PSC  primary sclerosing cholangitis  PSMD10  proteasome 26S subunit non-ATPase 10  PTEN  phosphatase and tensin homolog  PTPN14  tyrosine-protein phosphatase non-receptor type 14  RB  retinoblastoma protein  RECK  reversion-inducing cysteine-rich protein with Kazal motifs  RhoC  ras homolog family member C  ROC  receiver operating characteristic  Smad4  small mothers against decapentaplegic homolog 4  TET1  ten-eleven translocation 1  TGFβR2  transforming growth factor beta receptor 2  TIMP3  metalloproteinase inhibitor 3  TNFα  tumor necrosis factor alpha  TRAIL  TNF-related apoptosis-inducing ligand  UDCA  ursodeoxycholic acid  VEGF  vascular endothelial growth factor  XIAP  X-linked inhibitor of apoptosis protein  microRNAs  Extracellular vesicles  Cholangiopathies  Diagnosis  Pathogenesis  Therapy
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