Skin-Expressing lncRNAs in Inflammatory Responses

Abstract

Long non-coding RNAs (lncRNAs) have attracted attention for their potential roles in modulating keratinocyte differentiation and inflammatory response; however, for many identified skin-expressing lncRNAs, there is no comprehensive characterization regarding their biological roles. In addition, the reported expression profiles for lncRNAs can be ambiguous due to their low-expressing nature. The objective of this review is to utilize large scale genomic data to characterize the prominent skin-expressing lncRNAs, aiming to provide additional insights for their potential roles in the pathology of inflammatory skin of psoriasis and atopic dermatitis by integrating in vitro and in vivo data. We highlighted the different skin-expressing lncRNAs, including H19, which is significantly down-regulated in lesional skin of AD/psoriasis and upon cytokine stimulation in keratinocytes; it is also negatively correlated with CYP1A1 (r = -0.75, p = 8 × 10−73), a gene involved in drug metabolism and skin barrier homeostasis, in keratinocytes. In addition, SPRR2C, a potential regulator that modulates IL-22 stimulation, was upregulated in both atopic dermatitis and psoriasis lesional skin and was also downstream of the IL-17A and IL-17 + TNF signaling in keratinocytes. Using scRNAseq, we further revealed the cell type specificity of lncRNAs, including basal-expressing nature of H19 in the epidermis. Interestingly, instead of having cell type specific expression profile, we found few lncRNAs that are express across different cell types in skin, including MALAT1, NEAT1, and GAS5. While lncRNAs in general have lower expression, our results combining in vitro and in vivo experimental data demonstrate how some of these lncRNAs can play mediator roles in the cytokine-stimulated pathway.

Implications of LncRNAs and CircRNAs in psoriasis: a review

“…Similarly, Li et al identified a new lncRNA, WAKMAR1 (wound and keratinocyte migration-associated lncRNA 1), which regulated a network of protein-coding genes important for cell migration by interfering with E2F1 promoter methylation [ 31 ]. Recent studies identified numerous lncRNAs that are important in the pathology of the skin inflammatory response, for example, H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), NEAT1, and GAS5 [ 32 ].…”

“… [ 43 ] MALAT−1 Up DC/Macrophage/keratinocyte Inhibits lps-induced maturation of DCs; suppresses T cell proliferation and promotes production of treg cells; and inhibits inflammatory responses by interacting with intranuclear NF-κB in lps-stimulated macrophages. [ 32 , 44 , 45 ] FABPSP3 Up Skin/Keratinocyte It maintains KMT2C overexpression through recruitment of human antigen R (HuR) thereby enhancing its downstream response to proliferation and inflammation. [ 46 ] AGAP2-AS1 Up Skin/keratinocyte Upregulation of AKT 3 by sponge miR−424- 5 p activates the AKT/mTOR pathway, thereby promoting proliferation of keratinocytes.…”

Morinda officinalis extract exhibits protective effects against atopic dermatitis by regulating the MALAT1/miR‐590‐5p/CCR7 axis

“…Long noncoding RNAs (lncRNAs) are a class of RNA transcripts larger than 200 nucleotides that do not encode proteins, 13 and many studies has been reported that lncRNAs are abnormally expressed in a variety of specific diseases, 14,15 especially in AD 16 . For example, Wang et al uncover that lncRNAs humanlincRNA0016+ is associated with AD recurrence model, 17 and Shefler et al indicate that skin‐expressing lncRNAs are involved in the inflammatory of AD and psoriasis 18 . Notably, many studies have been reported that lncRNA MALAT1 plays a crucial role in various diseases by participating in the inflammatory response, such as ischemia–reperfusion injury, 19 diabetic, 20 sepsis, 21 otitis media, 22 and lung cancer 23 .…”

“…16 For example, Wang et al uncover that lncRNAs humanlincRNA0016+ is associated with AD recurrence model, 17 and Shefler et al indicate that skin-expressing lncRNAs are involved in the inflammatory of AD and psoriasis. 18 Notably, many studies have been reported that lncRNA MALAT1 plays a crucial role in various diseases by participating in the inflammatory response, such as ischemia-reperfusion injury, 19 diabetic, 20 sepsis, 21 otitis media, 22 and lung cancer. 23 Besides, Zhang et al illustrate that Morinda officinalis polysaccharide can regulate the expression of lncRNA and mRNA.…”

Editorial: The genetics of human Mendelian skin disorders

“…Therefore, several studies have combined the use of ultra-high multiplexed PCR and ligation-dependent probe amplification techniques with WES in the form of molecular diagnostics protocols for the identification of exon variants and the development of genetic profiles of patients with human Mendelian skin disorders. This includes the detection of ectodysplasin A exon variants in X-linked hypohidrotic ectodermal dysplasia Wang et al the genetic profiling of epidermolysis bullosa cases Alharthi et al and the discovery of a novel CREBBP variant for genetic diagnosis of Rubinstein–Taybi Syndrome Lee et al Recent evidence from large-scale expression studies (using microarrays and RNA sequencing) has also revealed the roles played by non-coding RNA molecules, such as small non-coding RNAs or miRNAs, in the pathogenesis of several complex skin diseases ( Shefler et al, 2022 ). The discovery and identification of such non-coding RNAs enables them to potentially serve as diagnostic markers.…”