P50 Noncoding small nucleolar RNA host genes as novel therapeutic targets in atopic dermatitis and psoriasis
Matteo Vietri RudanAbstract
Introduction and aims
Atopic dermatitis (AD) and psoriasis are common chronic inflammatory skin diseases characterized by abnormal keratinocyte proliferation and differentiation. Both diseases are associated with increases in different sets of cytokines, resulting in distinct but overlapping clinical features. Current therapies, such as systemic immunosuppressants, biologics and topical corticosteroids, have limitations owing to side effects and/or cost, highlighting the need for novel targeted treatments. Recent findings underscore the importance of noncoding RNAs in skin biology. MicroRNAs (miRNAs) are a type of noncoding RNAs that can modulate inflammation and keratinocyte behaviour in AD and/or psoriasis. A group of unusually highly expressed long noncoding RNAs called noncoding small nucleolar RNA host genes (ncSNHGs) can strongly stimulate keratinocytes to self-renew and inhibit their differentiation by affecting miRNA activity. In this study, we aim to investigate the potential of ncSNHGs as therapeutic targets for AD and/or psoriasis.
Methods
We analysed single-cell RNA sequencing datasets to assess the expression of ncSNHGs in the lesions of patients with AD and psoriasis and confirmed the expression results by in situ hybridization. We tested in silico the ability of lesions ncSNHGs to bind miRNAs that are relevant to the pathogenesis of AD and psoriasis.
Results
We found multiple ncSNHGs to be increased in both AD and psoriasis. Several of these lesional ncSNHGs are able to strongly affect keratinocyte proliferation and differentiation and are predicted to bind multiple miRNAs that have been implicated in AD and psoriasis.
Conclusions
Our preliminary results show that a subset of ncSNHGs are promising targets for the treatment of AD and psoriasis lesions. We are engineering models of AD and psoriasis using human skin equivalents challenged by different cytokine cocktails and generating primary keratinocyte lines that can be induced to downregulate epidermal ncSNHGs to further study their effectiveness and reliance on miRNA interactions.