PIWIL-2 and piRNAs are regularly expressed in epithelia of the skin and their expression is related to differentiation

Abstract

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.

Aberrantly Expressed Small Noncoding RNAome in Keloid Skin Tissue

“…The PIWI–piRNA system is part of tissue regeneration in salamanders ( Kim et al, 2018 ). PIWI protein could be involved in cell differentiation; it shows higher expression in skin appendages (e.g., sebaceous glands) compared with that in compartments in which stem cells are located ( Pammer et al, 2020 ). Here, we annotated multiple novel differential piRNAs in keloids, such as piR-38252 and hsa_piR_016659, two significantly differentially expressed piRNA subsets.…”

Imprinted small nucleolar RNAs: Missing link in development and disease?

“…DLK1‐DIO3 piRNAs are expressed in somatic tissues as well. piRNAs and associated protein PIWIL2 expression have been detected in keratinocytes and may be involved in epigenetic and transcriptomic regulation of target genes in the skin (Pammer et al, 2020). The piRNAs from this cluster are differentially expressed in several cancers, including bladder, lung, and head and neck squamous cell carcinomas (Chu et al, 2015; Enfield et al, 2016; Firmino et al, 2016).…”

The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas

“…Contrary to dogma, CTA expression is biased to gametes and cancer cells, but not restricted to them. Several CTAs, including brother of the regulator of imprinted sites (BORIS), piwi-like RNA mediated gene silencing 2 (PIWIL2) and heat shock protein 105 (HSP105) are expressed at low levels in healthy epidermal keratinocytes [ 97 , 98 , 99 , 100 ]. Their expression levels are altered in cancer (these CTAs are excluded from Table 1 ).…”