Down-Regulation of mir-424 Contributes to the Abnormal Angiogenesis via MEK1 and Cyclin E1 in Senile Hemangioma: Its Implications to Therapy
Open Access
- 14 December 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (12), e14334
- https://doi.org/10.1371/journal.pone.0014334
Abstract
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. 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. 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.Keywords
This publication has 40 references indexed in Scilit:
- MicroRNAs of the immune systemAnnals of the New York Academy of Sciences, 2010
- Basic fibroblast growth factor stimulates the proliferation of human dermal fibroblasts via the ERK1/2 and JNK pathwaysBritish Journal of Dermatology, 2009
- cAMP-mediated Induction of Cyclin E Sensitizes Growth-arrested Adipose Stem Cells to DNA Damage–induced ApoptosisMolecular Biology of the Cell, 2008
- Most mammalian mRNAs are conserved targets of microRNAsGenome Research, 2008
- Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangiomaNature Medicine, 2008
- Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5Blood, 2008
- The Human Angiotensin II Type 1 Receptor +1166 A/C Polymorphism Attenuates MicroRNA-155 BindingJournal of Biological Chemistry, 2007
- Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA TargetsCell, 2005
- Treatment of a venous-lake angioma with intense pulsed lightThe Lancet, 1998
- The effects of aging on the cutaneous microvasculatureJournal of the American Academy of Dermatology, 1995