title: Distinct miRNA profiles in normal and gastric cancer myofibroblasts and significance in Wnt signaling.
abstract: Stromal cells influence epithelial function in both health and disease. Myofibroblasts are abundant stromal cells that influence the cellular microenvironment by release of extracellular matrix (ECM) proteins, growth factors, proteases, cytokines, and chemokines. Cancer-associated myofibroblasts (CAMs) differ from adjacent tissue (ATMs) and normal tissue myofibroblasts (NTMs), but the basis of this is incompletely understood. We report now the differential expression of miRNAs in gastric cancer CAMs. MicroRNA arrays identified differences in the miRNA profile in gastric and esophageal NTMs and in CAMs from stomach compared with NTMs. miR-181d was upregulated in gastric CAMs. Analysis of differentially regulated miRNAs indicated an involvement in Wnt signaling. Examination of a microarray data set then identified Wnt5a as the only consistently upregulated Wnt ligand in gastric CAMs. Wnt5a stimulated miR-181d expression, and knockdown of miR-181d inhibited Wnt5a stimulation of CAM proliferation and migration. Analysis of miR-181d targets suggested a role in chemotaxis. Conditioned medium from CAMs stimulated gastric cancer cell (AGS) migration more than that from ATMs, and miR-181d knockdown reduced the effect of CAM-CM on AGS cell migration but had no effect on AGS cell responses to ATM conditioned media. The data suggest that dysregulation of miRNA expression in gastric CAMs, secondary to Wnt5a signaling, accounts at least in part for the effect of CAMs in promoting cancer cell migration.
authors.affiliation: Departments of Cellular and Molecular Physiology and.
authors.forename: Liyi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Departments of Cellular and Molecular Physiology and.
authors.forename: Islay
authors.initials: I
authors.lastname: Steele
authors.affiliation: Departments of Cellular and Molecular Physiology and.
authors.forename: Jothi Dinesh
authors.initials: JD
authors.lastname: Kumar
authors.affiliation: Departments of Cellular and Molecular Physiology and.
authors.forename: Rod
authors.initials: R
authors.lastname: Dimaline
authors.affiliation: Molecular and Clinical Cancer, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Puthen V
authors.initials: PV
authors.lastname: Jithesh
authors.affiliation: Department of Pathology, University of Szeged, Szeged, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tiszlavicz
authors.affiliation: Department of Pathology, University of Szeged, Szeged, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Reisz
authors.affiliation: Departments of Cellular and Molecular Physiology and.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Dockray
authors.affiliation: Departments of Cellular and Molecular Physiology and avarro@liv.ac.uk.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D058628:Myofibroblasts / Q000378:metabolism* / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein
keywords: Wnt5a; cancer; esophagus; miR-181d; myofibroblast; stomach