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Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders
The uc.291 transcript controls keratinocytes differentiation by physical interaction with ACTL6A and subsequent induction of transcription of the genes belonging to the epidermal differentiation complex (EDC). Uc.291 is also implicated in the dedifferentiation phenotype seen in poorly differentiated...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693168/ https://www.ncbi.nlm.nih.gov/pubmed/38041107 http://dx.doi.org/10.1186/s13062-023-00435-0 |
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author | Mancini, Mara Sergio, Simone Cappello, Angela Farkas, Timea Bernassola, Francesca Scarponi, Claudia Albanesi, Cristina Melino, Gerry Candi, Eleonora |
author_facet | Mancini, Mara Sergio, Simone Cappello, Angela Farkas, Timea Bernassola, Francesca Scarponi, Claudia Albanesi, Cristina Melino, Gerry Candi, Eleonora |
author_sort | Mancini, Mara |
collection | PubMed |
description | The uc.291 transcript controls keratinocytes differentiation by physical interaction with ACTL6A and subsequent induction of transcription of the genes belonging to the epidermal differentiation complex (EDC). Uc.291 is also implicated in the dedifferentiation phenotype seen in poorly differentiated cutaneous squamous cell carcinomas. Here, we would like to investigate the contribution of uc.291 to the unbalanced differentiation state of keratinocytes observed in hyperproliferative skin disorders, e. g., psoriasis. Psoriasis is a multifactorial inflammatory disease, caused by alteration of keratinocytes homeostasis. The imbalanced differentiation state, triggered by the infiltration of immune cells, represents one of the events responsible for this pathology. In the present work, we explore the role of uc.291 and its interactor ACTL6A in psoriasis skin, using quantitative real-time PCR (RT-qPCR), immunohistochemistry and bioinformatic analysis of publicly available datasets. Our data suggest that the expression of the uc.291 and of EDC genes loricrin and filaggrin (LOR, FLG) is reduced in lesional skin compared to nonlesional skin of psoriatic patients; conversely, the mRNA and protein level of ACTL6A are up-regulated. Furthermore, we provide evidence that the expression of uc.291, FLG and LOR is reduced, while ACTL6A mRNA is up-regulated, in an in vitro psoriasis-like model obtained by treating differentiated keratinocytes with interleukin 22 (IL-22). Furthermore, analysis of a publicly available dataset of human epidermal keratinocytes treated with IL-22 (GSE7216) confirmed our in vitro results. Taken together, our data reveal a novel role of uc.291 and its functional axis with ACTL6A in psoriasis disorder and a proof of concept that biological inhibition of this molecular axis could have a potential pharmacological effect against psoriasis and, in general, in skin diseases with a suppressed differentiation programme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00435-0. |
format | Online Article Text |
id | pubmed-10693168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106931682023-12-03 Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders Mancini, Mara Sergio, Simone Cappello, Angela Farkas, Timea Bernassola, Francesca Scarponi, Claudia Albanesi, Cristina Melino, Gerry Candi, Eleonora Biol Direct Research The uc.291 transcript controls keratinocytes differentiation by physical interaction with ACTL6A and subsequent induction of transcription of the genes belonging to the epidermal differentiation complex (EDC). Uc.291 is also implicated in the dedifferentiation phenotype seen in poorly differentiated cutaneous squamous cell carcinomas. Here, we would like to investigate the contribution of uc.291 to the unbalanced differentiation state of keratinocytes observed in hyperproliferative skin disorders, e. g., psoriasis. Psoriasis is a multifactorial inflammatory disease, caused by alteration of keratinocytes homeostasis. The imbalanced differentiation state, triggered by the infiltration of immune cells, represents one of the events responsible for this pathology. In the present work, we explore the role of uc.291 and its interactor ACTL6A in psoriasis skin, using quantitative real-time PCR (RT-qPCR), immunohistochemistry and bioinformatic analysis of publicly available datasets. Our data suggest that the expression of the uc.291 and of EDC genes loricrin and filaggrin (LOR, FLG) is reduced in lesional skin compared to nonlesional skin of psoriatic patients; conversely, the mRNA and protein level of ACTL6A are up-regulated. Furthermore, we provide evidence that the expression of uc.291, FLG and LOR is reduced, while ACTL6A mRNA is up-regulated, in an in vitro psoriasis-like model obtained by treating differentiated keratinocytes with interleukin 22 (IL-22). Furthermore, analysis of a publicly available dataset of human epidermal keratinocytes treated with IL-22 (GSE7216) confirmed our in vitro results. Taken together, our data reveal a novel role of uc.291 and its functional axis with ACTL6A in psoriasis disorder and a proof of concept that biological inhibition of this molecular axis could have a potential pharmacological effect against psoriasis and, in general, in skin diseases with a suppressed differentiation programme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00435-0. BioMed Central 2023-12-01 /pmc/articles/PMC10693168/ /pubmed/38041107 http://dx.doi.org/10.1186/s13062-023-00435-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Mancini, Mara Sergio, Simone Cappello, Angela Farkas, Timea Bernassola, Francesca Scarponi, Claudia Albanesi, Cristina Melino, Gerry Candi, Eleonora Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders |
title | Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders |
title_full | Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders |
title_fullStr | Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders |
title_full_unstemmed | Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders |
title_short | Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders |
title_sort | involvement of transcribed lncrna uc.291 in hyperproliferative skin disorders |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693168/ https://www.ncbi.nlm.nih.gov/pubmed/38041107 http://dx.doi.org/10.1186/s13062-023-00435-0 |
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