Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders

• Published in: Biology direct Vol. 18; no. 1; p. 82
• Main Authors: Mancini, Mara, Sergio, Simone, Cappello, Angela, Farkas, Timea, Bernassola, Francesca, Scarponi, Claudia, Albanesi, Cristina, Melino, Gerry, Candi, Eleonora
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.12.2023; BioMed Central; BMC
• Subjects: Actins - metabolism; Actins - pharmacology; ACTL6A; Analysis; Antibodies; Biopsy; Cell culture; Cell differentiation; Chromosomal Proteins, Non-Histone - metabolism; Datasets; De-differentiation; Development and progression; Diagnosis; Differentiation; Disorders; DNA-Binding Proteins; Epidermis; Epigenetics; Filaggrin; Gene loci; Genes; Genetic aspects; Genetic transcription; Homeostasis; Humans; Hyperproliferative skin disorders; Immune system; Immunohistochemistry; Inflammatory diseases; Interleukin 22; Interleukins; Keratinocytes; Keratinocytes - metabolism; Keratinocytes - pathology; lncRNA; Metabolism; Patients; Phenotypes; Physiological aspects; Psoriasis; Psoriasis - genetics; Psoriasis - metabolism; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - metabolism; Skin; Skin - metabolism; Skin - pathology; Skin diseases; Squamous cell carcinoma; Italy; United States > US; Epidermis; lncRNA; Psoriasis; De-differentiation; ACTL6A; Hyperproliferative skin disorders
• ISSN: 1745-6150; 1745-6150
• DOI: 10.1186/s13062-023-00435-0

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.