title: MiR-155 inhibits cell migration of human cardiomyocyte progenitor cells (hCMPCs) via targeting of MMP-16.
abstract: Undesired cell migration after targeted cell transplantation potentially limits beneficial effects for cardiac regeneration. MicroRNAs are known to be involved in several cellular processes, including cell migration. Here, we attempt to reduce human cardiomyocyte progenitor cell (hCMPC) migration via increasing microRNA-155 (miR-155) levels, and investigate the underlying mechanism. Human cardiomyocyte progenitor cells (hCMPCs) were transfected with pre-miR-155, anti-miR-155 or control-miR (ctrl-miR), followed by scratch- and transwell-assays. These functional assays displayed that miR-155 over-expression efficiently inhibited cell migration by 38 ± 3.6% and 59 ± 3.7% respectively. Conditioned medium from miR-155 transfected cells was collected and zymography analysis showed a significant decrease in MMP-2 and MMP-9 activities. The predicted 3'-UTR of MMP-16, an activator of MMP-2 and -9, was cloned into the pMIR-REPORT vector and luciferase assays were performed. Introduction of miR-155 significantly reduced luciferase activity which could be abolished by cotransfection with anti-miR-155 or target site mutagenesis. By using MMP-16 siRNA to reduce MMP-16 levels or by using an MMP-16 blocking antibody, hCMPC migration could be blocked as well. By directly targeting MMP-16, miR-155 efficiently inhibits cell migration via a reduction in MMP-2 and -9 activities. Our study shows that miR-155 might be used to improve local retention of hCMPCs after intramyocardial delivery.
authors.affiliation: Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Alain
authors.initials: A
authors.lastname: van Mil
authors.forename: Eissa N E
authors.initials: EN
authors.lastname: Aguor
authors.forename: Sailay
authors.initials: S
authors.lastname: Siddiqi
authors.forename: Krijn
authors.initials: K
authors.lastname: Vrijsen
authors.forename: Sridevi
authors.initials: S
authors.lastname: Jaksani
authors.forename: Corina
authors.initials: C
authors.lastname: Metz
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053513:Matrix Metalloproteinase 16 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection
chemical_list: C524942:MIRN155 microRNA, human; C507102:MMP16 protein, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D053513:Matrix Metalloproteinase 16; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9