LncRNA UCA1 negatively regulates NF‐kB activity in psoriatic keratinocytes through the miR125a‐A20 axis

Abstract

Psoriasis is one of the most common chronic inflammatory skin diseases that affects approximately 3% of the world's population. Hyper proliferation, infiltration of inflammatory cells and aberrant differentiation of keratinocytes are the three most important characteristics of psoriasis. Previous reports showed that NF‐κBis the crucial mediator linking psoriatic keratinocytes and immune cell states through its effects on chemokine and cytokine production. To identify the role of NF‐κB in psoriasis, we conducted ELISA assay to detect the activity of NF‐κB in lesional skin and nonlesional skin of patients with psoriasis. Mounting evidence suggests that the interaction between long noncoding RNAs (lncRNAs) and microRNAs plays important role in the regulation of the initiation and development of various diseases. In this article, we identified that lncRNA UCA1 was down‐regulated in lesional skin of patients with psoriasis. Further studies showed that lncRNA UCA1 could promote the expression of A20 by inhibitingmiR125a, and up‐regulated A20 decreased the activity of NF‐κB through its ubiquitin editing function. Taken together, we identified and demonstrated that lncRNA UCA1 negatively regulated NF‐κB activity in psoriasis through the miR125a‐A20 axis.

Skin-Expressing lncRNAs in Inflammatory Responses

“…When evaluating gene expression patterns in lesional compared to control skin, DANCR was upregulated and TINCR was downregulated in psoriasis lesional skin ( Figure 1A ). These findings support our current understanding of psoriasis as an inflammatory skin disease that is in part characterized by poor differentiation of keratinocytes ( Ma et al, 2021 ). Of importance, we discovered that TINCR was also downregulated in atopic dermatitis lesional skin—a finding that has not previously been reported.…”

“…It is also involved in cellular stress response and may play a role in psoriasis by decreasing sensitivity to keratinocyte apoptosis via the regulation of G1P3 ( Sonkoly et al, 2005 ; Zenz et al, 2005 ; Bari et al, 2011 ; Szegedi et al, 2012 ). Ma et al demonstrated that lncRNA UCA1 (urothelial carcinoma-associated 1) was downregulated in psoriatic lesional skin ( Ma et al, 2021 ). Initially named for its high expression in bladder cancer cells ( Roberson and Bowcock, 2010 ; Ma et al, 2021 ), UCA1 has now gained more attention regarding its role in psoriasis ( Ma et al, 2021 ).…”

“…Ma et al demonstrated that lncRNA UCA1 (urothelial carcinoma-associated 1) was downregulated in psoriatic lesional skin ( Ma et al, 2021 ). Initially named for its high expression in bladder cancer cells ( Roberson and Bowcock, 2010 ; Ma et al, 2021 ), UCA1 has now gained more attention regarding its role in psoriasis ( Ma et al, 2021 ). Specifically, it upregulates the expression of cytoplasmic zinc finger protein A20 (TNFAIP3, TNFα induced protein 3) by inhibiting microRNA125a ( Ma et al, 2021 ).…”

“…Initially named for its high expression in bladder cancer cells ( Roberson and Bowcock, 2010 ; Ma et al, 2021 ), UCA1 has now gained more attention regarding its role in psoriasis ( Ma et al, 2021 ). Specifically, it upregulates the expression of cytoplasmic zinc finger protein A20 (TNFAIP3, TNFα induced protein 3) by inhibiting microRNA125a ( Ma et al, 2021 ). Through the miRNA125a-A20 axis, UCA1 negatively regulates the activity of NF B ( Li et al, 2015 ; Ma et al, 2021 ).…”

“…Specifically, it upregulates the expression of cytoplasmic zinc finger protein A20 (TNFAIP3, TNFα induced protein 3) by inhibiting microRNA125a ( Ma et al, 2021 ). Through the miRNA125a-A20 axis, UCA1 negatively regulates the activity of NF B ( Li et al, 2015 ; Ma et al, 2021 ). Other lncRNAs that have revealed roles in psoriasis include lncRNA RP6-65G23.1 , lncRNA MSX2P (cytoplasmic lncRNA Msh homeobox 2 pseudogene 1), and lncRNA GAS5 (growth arrest specific 5).…”