Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: its implications to therapy.
Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: its implications to therapy.
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DOI：
10.1371/journal.pone.0014334
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发表时间：
2010-12-14
期刊：
影响因子：
3.7
通讯作者：
Ihn H
中科院分区：
文献类型：
--
作者：
Nakashima T;Jinnin M;Etoh T;Fukushima S;Masuguchi S;Maruo K;Inoue Y;Ishihara T;Ihn H
老年性血管瘤，又称樱桃状血管瘤，是老年皮肤最常见的血管畸形。其异常血管生成的发病机制尚不清楚。在本研究中，我们发现老年性血管瘤由真皮上层的一簇增生的小血管通道组成，表明这种肿瘤属于血管性肿瘤。我们随后研究了老年性血管瘤内皮细胞增殖的机制，重点是microRNA（miRNA）。miRNA-PCR芯片分析显示，老年性血管瘤中mir-424的表达水平低于其他血管畸形。与正常皮肤或其他异常相比，mir-424的预测靶基因MEK 1和cyclin E1在老年性血管瘤中的蛋白表达增加，但其mRNA水平没有增加。用特异性抑制剂抑制正常人皮肤微血管内皮细胞（HDMECs）中mir-424的表达，可导致MEK 1和cyclin E1蛋白表达增加，而mRNA水平不受抑制剂的影响。mir-424的特异性抑制剂也能显著诱导HDMECs的增殖，而MEK 1或cyclin E1的siRNA转染则使HDMECs的细胞数减少。结论：老年性血管瘤中mir-424表达降低，MEK 1或cyclin E1表达升高，可能导致肿瘤细胞异常增殖。老年性血管瘤是研究皮肤血管生成的良好模型。研究老年性血管瘤的发生机制以及miRNA对老年皮肤血管生成的调控机制，可能为利用miRNA转染老年性血管瘤提供新的治疗方法。
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.
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1161/atvbaha.107.150284
发表时间：
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作者：
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作者：
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