title: Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: its implications to therapy.
abstract: BACKGROUND
  Senile hemangioma, so-called cherry angioma, is known as the most common vascular anomalies specifically seen in the aged skin. The pathogenesis of its abnormal angiogenesis is still unclear.
  
  
  RESULTS
  In this study, we found that senile hemangioma consisted of clusters of proliferated small vascular channels in upper dermis, indicating that this tumor is categorized as a vascular tumor. We then investigated the mechanism of endothelial proliferation in senile hemangioma, focusing on microRNA (miRNA). miRNA PCR array analysis revealed the mir-424 level in senile hemangioma was lower than in other vascular anomalies. Protein expression of MEK1 and cyclin E1, the predicted target genes of mir-424, was increased in senile hemangioma compared to normal skin or other anomalies, but their mRNA levels were not. The inhibition of mir-424 in normal human dermal microvascular ECs (HDMECs) using specific inhibitor in vitro resulted in the increase of protein expression of MEK1 or cyclin E1, while mRNA levels were not affected by the inhibitor. Specific inhibitor of mir-424 also induced the cell proliferation of HDMECs significantly, while the cell number was decreased by the transfection of siRNA for MEK1 or cyclin E1.
  
  
  CONCLUSIONS
  Taken together, decreased mir-424 expression and increased levels of MEK1 or cyclin E1 in senile hemangioma may cause abnormal cell proliferation in the tumor. Senile hemangioma may be the good model for cutaneous angiogenesis. Investigation of senile hemangioma and the regulatory mechanisms of angiogenesis by miRNA in the aged skin may lead to new treatments using miRNA by the transfection into senile hemangioma.
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Nakashima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Jinnin
authors.forename: Tomomi
authors.initials: T
authors.lastname: Etoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukushima
authors.forename: Shinichi
authors.initials: S
authors.lastname: Masuguchi
authors.forename: Keishi
authors.initials: K
authors.lastname: Maruo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inoue
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D000368:Aged; D002460:Cell Line; D019927:Cyclin E / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006391:Hemangioma / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000096:biosynthesis*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D015513:Oncogene Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; C554214:MIRN424 microrna, human; D035683:MicroRNAs; D015513:Oncogene Proteins; D012333:RNA, Messenger; D048369:MAP Kinase Kinase 1