Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
PLoS One. 2012;7(11):e49568. doi: 10.1371/journal.pone.0049568. Epub 2012 Nov 14.
Vascular endothelial growth factor A (VEGFA) plays a key role in the angiogenesis of human skin. Elevated levels of VEGFA are associated with several pathological conditions, including chronic inflammatory skin diseases and several types of skin cancer. In particular, squamous cell carcinoma (SCC) of the skin, the second most common skin cancer in the general population, is characterized by invasive growth, pronounced angiogenesis and elevated levels of VEGFA. The processing, turnover and production of VEGFA are extensively regulated at the post-transcriptional level, both by RNA-binding proteins and microRNAs (miRNAs). In the present study, we identified a new miRNA recognition element in a downstream conserved region of the VEGFA 3'-UTR. We confirmed the repressive effect of miR-361-5p on this element in vitro, identifying the first target for this miRNA. Importantly, we found that miR-361-5p levels are inversely correlated with VEGFA expression in SCC and in healthy skin, indicating that miR-361-5p could play a role in cancers.
血管内皮生长因子 A(VEGFA)在人类皮肤的血管生成中起着关键作用。VEGFA 水平升高与几种病理状况有关,包括慢性炎症性皮肤病和几种皮肤癌。特别是皮肤鳞状细胞癌(SCC),是普通人群中第二常见的皮肤癌,其特征为侵袭性生长、明显的血管生成和 VEGFA 水平升高。VEGFA 的加工、周转和产生在转录后水平受到广泛调节,包括 RNA 结合蛋白和 microRNAs(miRNAs)。在本研究中,我们在 VEGFA 3'UTR 的下游保守区域中鉴定出一个新的 miRNA 识别元件。我们在体外证实了 miR-361-5p 对该元件的抑制作用,鉴定了该 miRNA 的第一个靶标。重要的是,我们发现 miR-361-5p 的水平与 SCC 和健康皮肤中的 VEGFA 表达呈负相关,表明 miR-361-5p 可能在癌症中发挥作用。