Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
Exp Dermatol. 2010 Mar;19(3):269-78. doi: 10.1111/j.1600-0625.2010.01066.x.
Psoriasis Susceptibility-Related RNA Gene Induced by Stress (PRINS) is a non-coding RNA overexpressed in lesional and non-lesional psoriatic epidermis and induced by stress. Its function in healthy and psoriatic skin is still not known. Here, we report that PRINS regulates G1P3, a gene with anti-apoptotic effects in keratinocytes. siRNA-mediated inhibition of PRINS gene resulted in altered cell morphology and gene expression alterations, as demonstrated in a microarray experiment. One of the genes regulated by PRINS ncRNA was G1P3, an interferon-inducible gene with anti-apoptotic effects in cancer cells. Interestingly, we found that G1P3 was 400-fold upregulated in hyperproliferative lesional and ninefold upregulated in non-lesional psoriatic epidermis compared to healthy epidermis. In vitro, G1P3 protein levels were highest in proliferating keratinocytes and siRNA-mediated downregulation of G1P3 resulted in increased cell apoptosis. These data indicate that G1P3 inhibits spontaneous keratinocyte apoptosis and hence its high expression in psoriatic skin may contribute to the development of psoriatic lesions. We hypothesize that the deregulation of the PRINS ncRNA may contribute to psoriasis and results in decreased sensitivity to spontaneous keratinocyte apoptosis via the regulation of G1P3.
压力诱导的银屑病易感相关 RNA 基因（PRINS）是一种在病变和非病变银屑病表皮中过度表达的非编码 RNA，由压力诱导。其在健康和银屑病皮肤中的功能尚不清楚。在这里，我们报告 PRINS 调节 G1P3，这是一种在角质细胞中具有抗凋亡作用的基因。siRNA 介导的 PRINS 基因抑制导致细胞形态改变和基因表达改变，如微阵列实验所示。受 PRINS ncRNA 调节的基因之一是 G1P3，这是一种干扰素诱导的基因，在癌细胞中具有抗凋亡作用。有趣的是，我们发现与健康表皮相比，G1P3 在过度增殖的病变表皮中上调了 400 倍，在非病变银屑病表皮中上调了 9 倍。在体外，增殖角质细胞中 G1P3 蛋白水平最高，siRNA 介导的 G1P3 下调导致细胞凋亡增加。这些数据表明，G1P3 抑制自发的角质细胞凋亡，因此其在银屑病皮肤中的高表达可能有助于银屑病皮损的发展。我们假设 PRINS ncRNA 的失调可能导致银屑病，并通过调节 G1P3 导致对自发角质细胞凋亡的敏感性降低。
