LncRNA UCA1 promotes keratinocyte inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis

Abstract

Psoriatic inflammation can be regulated by epigenetic factors, but little is known about their role. This work aims to reveal the effects of lncRNA UCA1 in keratinocyte inflammation. UCA1 was a psoriasis-related lncRNA in eight GEO transcriptome datasets and psoriatic skin. When we over-expressed or knocked down UCA1 in the keratinocyte cell line (HaCaT), the transcriptome and proteomic data showed that UCA1 could positively regulate inflammatory functions, such as response to cytokine. Experimental findings confirmed that UCA1 could increase inflammatory cytokine secretion, innate immunity gene expression, and ability of vascular endothelial cells. Besides, UCA1 could activate the NF-κB signaling pathway, which might be the target of UCA1-incuded HIF-1α and STAT3. We then uncovered the direct interactions between UCA1 and N6-methyladenosine (m6A) methyltransferase METTL14. METTL14 proved to be a functional suppressor of inflammation, it could antagonize the functions of UCA1. Subsequently, we found the m6A levels of HIF-1α were decreased in psoriatic lesions, thus HIF-1α could be the target of METTL14. In general, this work indicates that UCA1 can positively regulate keratinocytes inflammation and psoriasis development, it binds METTL14 and then activates HIF-1α and NF-κB signaling pathway. Our work presents a new understanding of UCA1 and METTL14 in psoriatic inflammation.

m6A‐ and m5C‐ modified lncRNAs orchestrate the prognosis in cutaneous melanoma and m6A‐ modified LINC00893 regulates cutaneous melanoma cell metastasis

“…also showed that the inhibition of PVT1 exon 2 could induce the growth suppression of cutaneous squamous cell carcinoma, which was caused by cellular senescence, increased p21/CDKN1A expression and cell cycle arrest 36 . However, besides skin tumors, lncRNAs also influence the pathogenesis of many skin inflammatory diseases, 33 such as psoriasis, 38–41 hidradenitis suppurativa, 42,43 atopic dermatitis 44–46 . Among these skin diseases, the psoriasis was the most studied one.…”

“…Among these skin diseases, the psoriasis was the most studied one. LncRNAs including lncRNA UCA1, 38 lncRNA BLACAT1 39 and LINC00958 41 could affect the destination of keratinocytes and then determine the process of psoriasis. Therefore, lncRNAs not only play a role in cutaneous carcinogenesis but influence the pathogenesis of non‐tumorous skin diseases.…”