title: Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma.
abstract: Infantile hemangioma (IH) is the most common vascular tumor of infancy, and it uniquely regresses in response to oral propranolol. MicroRNAs (miRNAs) have emerged as key regulators of vascular development and are dysregulated in many disease processes, but the role of miRNAs in IH growth has not been investigated. We report expression of C19MC, a primate-specific megacluster of miRNAs expressed in placenta with rare expression in postnatal tissues, in glucose transporter 1-expressing (GLUT-1-expressing) IH endothelial cells and in the plasma of children with IH. Tissue or circulating C19MC miRNAs were not detectable in patients having 9 other types of vascular anomalies or unaffected children, identifying C19MC miRNAs as the first circulating biomarkers of IH. Levels of circulating C19MC miRNAs correlated with IH tumor size and propranolol treatment response, and IH tissue from children treated with propranolol or from children with partially involuted tumors contained lower levels of C19MC miRNAs than untreated, proliferative tumors, implicating C19MC miRNAs as potential drivers of IH pathogenesis. Detection of C19MC miRNAs in the circulation of infants with IH may provide a specific and noninvasive means of IH diagnosis and identification of candidates for propranolol therapy as well as a means to monitor treatment response.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, University of Washington, Seattle, Washington, USA.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Strub
authors.affiliation: Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kirsh
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, University of Washington, Seattle, Washington, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Whipple
authors.affiliation: Laboratory for Innovative Translational Technologies, Harvard Medical School, Boston, Massachusetts, USA.|Predicine Inc., Hayward, California, USA.
authors.forename: Winston P
authors.initials: WP
authors.lastname: Kuo
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Keller
authors.affiliation: Department of Laboratories, Seattle Children's Hospital (SCH), Seattle, Washington, USA.
authors.forename: Raj P
authors.initials: RP
authors.lastname: Kapur
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Majesky
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, University of Washington, Seattle, Washington, USA.|Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Perkins