Pammer Johannes, Rossiter Heidi, Bilban Martin, Eckhart Leopold, Buchberger Maria, Monschein Laura, Mildner Michael
Clinical Institute of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Arch Dermatol Res. 2020 Dec;312(10):705-714. doi: 10.1007/s00403-020-02052-7. Epub 2020 Mar 12.
PIWI proteins play multiple roles in germline stem cell maintenance and self-renewal. PIWI-interacting RNAs (piRNAs) associate with PIWI proteins, form effector complexes and maintain genome integrity and function in the regulation of gene expression by epigenetic modifications. Both are involved in cancer development. In this study, we investigated the expression of PIWIL-2 and piRNAs in normal human skin and epithelial tumors and its regulation during keratinocyte (KC) differentiation. Immunohistochemistry showed that PIWIL-2 was regularly expressed in the epidermis and adnexal tissue with strongest expression in sebaceous glands. Cell culture studies revealed an association of PIWIL-2 expression with the state of differentiated KC. In contrast, the PIWIL-2 expression pattern did not correlate with stem cell compartments or malignancy. piRNAs were consistently detected in KC in vitro by next-generation sequencing and the expression levels of numerous piRNAs were regulated during KC differentiation. Epidermal piRNAs were predominantly derived from processed snoRNAs (C/D-box snoRNAs), tRNAs and protein coding genes. Our data indicate that components of the PIWIL-2-piRNA pathway are present in epithelial cells of the skin and are regulated in the context of KC differentiation, suggesting a role of somatic gene regulation. However, putative roles in the maintenance of stem cell compartments or the development of malignancy in the skin were not supported by this study.
PIWI蛋白在生殖系干细胞的维持和自我更新中发挥多种作用。PIWI相互作用RNA（piRNA）与PIWI蛋白结合，形成效应复合物，并通过表观遗传修饰在基因表达调控中维持基因组的完整性和功能。二者均与癌症发展有关。在本研究中，我们调查了PIWIL-2和piRNA在正常人类皮肤和上皮肿瘤中的表达情况，以及它们在角质形成细胞（KC）分化过程中的调控。免疫组织化学显示，PIWIL-2在表皮和附属器组织中正常表达，在皮脂腺中表达最强。细胞培养研究揭示了PIWIL-2表达与KC分化状态之间的关联。相比之下，PIWIL-2的表达模式与干细胞区室或恶性肿瘤无关。通过下一代测序在体外KC中持续检测到piRNA，并且在KC分化过程中许多piRNA的表达水平受到调控。表皮piRNA主要来源于加工后的小核仁RNA（C/D盒小核仁RNA）、转运RNA和蛋白质编码基因。我们的数据表明，PIWIL-2-piRNA途径的成分存在于皮肤上皮细胞中，并在KC分化的背景下受到调控，提示其在体细胞基因调控中的作用。然而，本研究不支持其在维持干细胞区室或皮肤恶性肿瘤发展中的假定作用。
