title: MiR-886-3p down regulates CXCL12 (SDF1) expression in human marrow stromal cells.
abstract: Stromal Derived Factor 1 (SDF1 or CXCL12), is a chemokine known to be critical for the migration of cells in several tissue systems including the homing of the hematopoietic stem cell (HSC) to its niche in the bone marrow. A comparative analysis of miRNA expression profiles of two stromal cell lines, distinguishable by function and by CXCL12 expression (CXCL12+ and CXCL12-), revealed that the CXCL12- cells expressed>40 fold more miR-886-3p than the CXCL12+ cells. Screening studies showed that when miR-886-3p was transfected into the CXCL12+ stromal cells, the expression of CXCL12 was down-regulated by as much as 85% when compared to appropriate controls, and results in the loss of CXCL12-directed chemotaxis. Similar reductions in CXCL12 were obtained with the transfection of miR-886-3p into primary stromal cell cultures. Additional studies showed that miR-886-3p specifically targeted the 3' untranslated region (UTR) of CXCL12 mRNA. These data suggest a role for miRNA in modulating the expression of CXCL12, a gene product with a critical role in hematopoietic regulation.
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America. Manoj.Pillai@UCDenver.edu
authors.forename: Manoj M
authors.initials: MM
authors.lastname: Pillai
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yang
authors.forename: Ilango
authors.initials: I
authors.lastname: Balakrishnan
authors.forename: Lynne
authors.initials: L
authors.lastname: Bemis
authors.forename: Beverly
authors.initials: B
authors.lastname: Torok-Storb
mesh_terms: D020413:3' Untranslated Regions; D001854:Bone Marrow Cells / Q000166:cytology*; D051929:CD146 Antigen / Q000096:biosynthesis; D002460:Cell Line; D002469:Cell Separation; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006801:Humans; D008024:Ligands; D035683:MicroRNAs / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D020413:3' Untranslated Regions; D051929:CD146 Antigen; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D008024:Ligands; C559060:MIRN886 microRNA, human; D035683:MicroRNAs