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Heat Map showing a distinguishable expression profile of circular RNAs (circRNAs) between the two groups. The values correspond to the different colors representing the fold change (log2 transformed) of each sample. Black stands for 0, indicating no change in gene expression; red represents upregulation, and green represents down-regulation; the brightness of the color represents the degree of increased or decreased gene expression.
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Background/aims:
Circular RNAs (circRNAs) are evolutionary conserved circular non-coding RNAs that play a role in several diseases by sequestering (sponging) microRNAs (miRNAs). However, their role in psoriasis remains unclear. In the present study, we investigated the expression of circRNAs and analyzed their potential functions in psoriasis.
Me...
Context in source publication
Context 1
... tissues was displayed in a scatter plot of the circRNA expression profile (Fig. 1C). In addition, a volcano plot identified differentially expressed circRNAs at different P-values and fold-changes between the two groups ( Fig. 1D). Hierarchical clustering revealed that the circRNA expression levels were distinguishable in the associated heat map (Fig. 2). The analysis identified a set of 4956 differentially expressed circRNAs (Supplementary Table S1 -for all supplementary material see www.karger.com/10.1159/000493952/). The distribution of dysregulated circRNAs on human chromosomes is shown in Fig. 3. Among all the differential expressed circRNAs, Table 2. Specific primer sequences for ...
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Heart failure (HF) is a deadly disease that is difficult to accurately diagnose. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that might play important roles in many cardiovascular diseases. However, their role in HF remains unclear. CircRNA microarrays were performed on plasma samples obtained from three patients with HF and three...
Citations
... During the past decades, some advances in circRNAs research laboratory work are focusing on the circRNA-miRNA-mRNA regulatory mechanism, whereby miRNA captured by cytoplasmic exonic circRNAs are unable to bind to their target mRNAs and thereby lose the ability to constrain gene expression, ultimately leading to a rise in target mRNA levels [9,30]. Furthermore, it has been reported that this regulatory mechanism is deeply involved in the regulation of psoriasis pathogenesis [32]. Herein, the online bioinformatics tools unveiled that there exist some binding sites between circ_0056856 and miR-197-3p in the HaCaT cell line. ...
Background
Psoriasis is a chronic inflammation-associated skin disorder, and interleukin-22 (IL-22) is involved in psoriasis pathogenesis by boosting the proliferation and migration of keratinocytes. Mounting evidence has shown that circRNAs might play an important role in several aspects of psoriasis. This study is designed to explore the role and mechanism of circ_0056856 in regulating the phenotypes of IL-22-induced keratinocytes (HaCaT cells).
Methods
Circ_0056856, microRNA-197-3p (miR-197-3p), Cyclin-dependent kinase 1 (CDK1), and Wilms tumor 1-associated protein (WTAP) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, migration, and invasion were analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), Wound scratch, and Transwell assays. After being predicted by Circinteractome or TargetScan, binding between miR-197-3p and circ_0056856 or CDK1 was verified by a dual-luciferase reporter assay. CDK1 and WTAP protein levels were determined using Western blot. Interaction between WTAP and circ_0056856 was assessed using methylated RNA immunoprecipitation (MeRIP) assay.
Results
Increased circ_0056856, CDK1, and WTAP were observed in psoriasis patients and IL-22-treated HaCaT cells. Moreover, circ_0056856 knockdown might repress IL-22-induced HaCaT cell proliferation, migration, and invasion in vitro. In mechanism, circ_0056856 might function as a sponge of miR-197-3p to modulate CDK1 expression, and WTAP improved circ_0056856 expression via m6A methylation.
Conclusion
WTAP-guided m6A modified circ_0056856 facilitates IL-22-stimulated HaCaT cell damage through the miR-197-3p/CDK1 axis, which could provide novel insights into psoriasis treatment.
... An expanding number of researchers suggest that dysregulation of circRNA is closely linked to severe diseases, including, but not limited to, autoimmune diseases. Previous studies demonstrate associated circRNA expression in psoriasis, regardless of the presence of skin lesions [54,55]. ...
Psoriasis is a chronic inflammatory skin disease, the prevalence of which is increasing. Genetic, genomic, and epigenetic changes play a significant role in the pathogenesis of psoriasis. This review summarizes the impact of epigenetics on the development of psoriasis and highlights challenges for the future. The development of epigenetics provides a basis for the search for genetic markers associated with the major histocompatibility complex. Genome-wide association studies have made it possible to link psoriasis to genes and therefore to epigenetics. The acquired knowledge may in the future serve as a solid foundation for developing newer, increasingly effective methods of treating psoriasis. In this narrative review, we discuss the role of epigenetic factors in the pathogenesis of psoriasis.
... Importantly, circRNAs could act as competitive endogenous RNAs (ceRNAs) to sponge off and regulate miRNAs on their target genes [10][11][12]. As reported, circRNAs played a considerable regulatory role in various diseases and were involved in the pathogenesis and progression of inflammatory skin disorders by distinct molecular mechanisms [13][14][15]. For example, hsa_circ_0061012 participated in psoriasis in response to NF-κB nuclear import regulations and T cell selection, which may be a potential biomarker for psoriasis [14]. ...
... As reported, circRNAs played a considerable regulatory role in various diseases and were involved in the pathogenesis and progression of inflammatory skin disorders by distinct molecular mechanisms [13][14][15]. For example, hsa_circ_0061012 participated in psoriasis in response to NF-κB nuclear import regulations and T cell selection, which may be a potential biomarker for psoriasis [14]. Additionally, transcriptional profiling of circRNAs in severe acne and adjacent to the patient's normal skin tissues showed that 538 differently expressed of circRNAs were associated with the occurrence and development of acne [16]. ...
... CircRNAs were single-stranded covalent RNA molecules, which involved in occurrence, progression, and prognosis of different diseases [37][38][39][40]. Besides, it was supposed that dysregulation of circRNAs might contribute to inflammatory skin diseases [14,15,41]. Clinically, C. acnes infection caused skin inflammation [42][43][44], while whether circRNAs exerted biological functions in the process was unclear. ...
Introduction:
CircRNAs are closely related to many human diseases, however, their role in acne remains unclear. This study aimed to determine the role of hsa-circ_0102678 in regulating inflammation of acne.
Methods:
Firstly, microarray analysis was performed to study the expression of circRNAs in acne. Subsequently, RNase R digestion assay and FISH assay were utilized to confirm the characteristics of hsa-circ_0102678. Finally, qRT-PCR, Western blotting analysis, Immunoprecipitation, Luciferase reporter assay, circRNA probe pull-down assay, Biotin-labeled miRNA pull-down assay, RNA immunoprecipitation (RIP) assay and m6A dot blot assay were utilized to reveal the functional roles of hsa-circ_0102678 on inflammation induced by C. acnes biofilm in human primary keratinocytes.
Results:
Our investigations showed that the expression of hsa-circ_0102678 was significantly decreased in acne tissues and hsa-circ_0102678 was a type of circRNAs, which was mainly localized in the cytoplasm of primary human keratinocytes. Moreover, hsa-circ_0102678 remarkably affected the expression of IL-8, IL-6, and TNF-α, which induced by C. acnes biofilm. Importantly, mechanistic studies indicated that the YTHDC1 could bind directly to hsa-circ_0102678 and promote the export of N6-methyladenosine modified hsa-circ_0102678 to the cytoplasm. Besides, hsa-circ_0102678 could bind to miR-146a and sponge miR-146a to promote the expression of IRAK1 and TRAF6.
Conclusion:
Our findings revealed a previously unknown process by which hsa_circ_0102678 promoted keratinocyte inflammation induced by C. acnes biofilm via regulating miR-146a/TRAF6 and IRAK1 axis.
... Some circRNAs, such as circRAB3B, which prevents keratinocyte hyper-proliferation through the upregulation of the tumor suppressor gene PTEN, are less abundant in psoriatic skin compared to nonlesional and healthy skin [98]. Conversely, circOAS3 [99], circEIF5 [100], circ_0060531 [101], hsa_circ_0003738 [102], or hsa_circ_0061012 [103] are upregulated in psoriasis. ...
Psoriasis is a disease involving the innate and adaptative components of the immune system, and it is triggered by environmental factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, especially in genome and epigenome-wide studies, have provided a better understanding of the genetic and epigenetic mechanisms to determine the physiopathology of psoriasis and facilitate the development of new drugs. This review intends to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.
... Some circRNAs, such as circRAB3B, which prevents keratinocyte hyper-proliferation through the upregulation of the tumor suppressor gene PTEN, are less abundant in psoriatic skin compared to non-lesional and healthy skin [111]. Conversely, circOAS3 [112], circEIF5 [113], circ_0060531 [114], hsa_circ_0003738 [115], or hsa_circ_0061012 [116] are upregulated in psoriasis. ...
Psoriasis is considered an immune-mediated disease involving the innate and adaptative immune system triggered by environmental risk factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, specially genome and epigenome-wide studies, have allowed a more sensitive study of the genetic and epigenetic mechanisms, allowing an enhanced understanding of its physiopathology and facilitating the development of new drugs. In this review, we aim to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.
... Although there are few reports on circRNAs in psoriasis research, current studies demonstrated a distinguished circRNA expression landscape of psoriasis lesions from both non-lesional and healthy skins [18,19]. ...
... In skin diseases, circRNAs were associated with melanoma occurrence, progression, and tumour malignant behaviours, which included metastasis and invasion [91,92]. RNAseq identified many differentially expressed circRNAs in psoriasis, and some circRNAs may be candidate biomarkers or involved in psoriasis pathogenesis [19,93]; several circRNAs may contribute to the development and pathophysiology of hypertrophic scars [94,95]. In this section, we review the current understanding of circRNA biology and circRNA functions in relation to psoriasis. ...
... CircRNAs are key in regulating cell proliferation, the immune system, and the inflammatory response [89,115,116]. An increasing number of studies have proven that many circRNAs are abnormally expressed between psoriatic lesions and normal healthy skin tissues [18,19,[117][118][119], and might be involved in psoriasis occurrence and development through a variety of molecular mechanisms, which provide more evidence that circRNAs are potential novel therapeutic targets and biomarkers for psoriasis diagnosis, prognosis, and therapy. ...
Psoriasis is a chronic inflammatory skin disease characterized by skin infiltration of immune cells and abnormal epidermal thickening. The initial pathogenesis has not been fully elucidated. Non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs) and circular RNAs (circRNAs), comprise the majority of genome transcripts and are important influencers of gene transcription and post-transcription modulations. Emerging roles of ncRNAs in psoriasis were identified recently. This review summarizes the existing studies of psoriasis-related lncRNAs and circRNAs. A considerable proportion of the studied lncRNAs and circRNAs regulate keratinocyte mobility, such as keratinocyte proliferation and differentiation. Some lncRNAs and circRNAs are tightly related to keratinocyte inflammation reactions. Other reports demonstrated that they are also implicated in modulating immune cell differentiation, proliferation, and activation. This review might illuminate future psoriasis research and highlight that lncRNAs and circRNAs might act as therapeutic targets.
... In the last few years, several differentially expressed circRNAs, e.g., hsa_circ_0061012, hsa_circ_0003689, chr4:121,675,708|121,732,604, and hsa_circ_0003718, have been identified in psoriatic lesions compared to normal skin tissues (Qiao et al. 2018;Liu et al. 2019b) (Table 2). In silico analysis suggested their potential involvement in psoriasis pathogenesis; however, functional validation of these differentially expressed circRNAs remains an open problem. ...
... Liver X receptor-α (LXR-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) prevent keratinocyte hyper-proliferation in healthy skin. MiR-203 (Qiao et al. 2018) directly targets LXR-α and PPAR-γ, resulting in their downregulation in psoriatic lesions thereby causing keratinocyte hyper-proliferation (Xiao et al. 2020). Another upregulated miRNA in psoriasis, miR-31, induces hyper-proliferation of basal keratinocytes by targeting protein phosphatase 6 (PPP6), a negative regulator of the G1/S transition of the cell cycle (Yan et al. 2015). ...
Psoriasis is a complex genetic skin disorder typically manifested by red, scaly, and itchy plaques most commonly over the scalp, trunk, elbows, and knees. Histopathological features include thickening of the epidermal layer due to hyper-proliferation and abnormal differentiation of epidermal keratinocytes along with infiltration of immune cells in the psoriatic skin. It is a chronic inflammatory relapsing disease, and there is currently no permanent cure for psoriasis. Proper medications can reduce the severity of the disease and improve the quality of life of the patients. While the genetic components of psoriasis pathogenesis are well explored, the full understanding of its epigenetic component remains elusive. Non-coding RNAs (ncRNAs) are documented to regulate various epigenetic processes that lead to the pathogenesis of different diseases including psoriasis. In this review, we have discussed the molecular interplay of different ncRNAs in psoriasis pathogenesis. The roles of microRNAs (miRNAs) in psoriasis are pretty well studied, whereas the roles of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are emerging. This review provides ideas covering some of the latest findings of different modes of functions played by those different ncRNAs documented in the literature. As an ever-evolving topic, some works are still ongoing as well as there are several fields that need rigorous scientific ventures. We have proposed the areas which claim more explorations to better understand the roles played by the ncRNAs in psoriasis pathogenesis.
... It is signi cant to note that circRNAs may function as competitive endogenous RNAs (ceRNAs) that regulate and sponge miRNAs on their target genes. According to reports, circRNAs has signi cant regulatory functions in several illnesses and are connected to the pathophysiology and development of in ammatory skin conditions through diverse molecular pathways [10][11][12]. For example, Lower-level expression of hsa_circ_0045272 in T-cells of patients with systemic lupus erythematosus, which contains miR-6127 binding sites and regulates downwards DTX4 and PAX8 [13]. ...
... It is widely accepted that the development and occurrence of acne are caused by cellular in ammation [18,22,23]. During this time, circRNAs are emerging as an important moderator controlling cell in ammation in many human diseases [11,12,24,25]. However, circRNAs has not been investigated in the pathophysiology of acne ...
... CircRNAs are single stranded covalently RNA molecules, which connect with occurrence and development of different diseases [26][27][28]. Moreover, it is supposed that dysregulation of circRNAs may be a factor in in ammatory skin illnesses [11][12][13]. Clinically, the C. acnes infection, which causes skin in ammation, is one of the causes of acne. It is not clear, however, if circRNAs has physiologic effects on acne. ...
Background
Circular RNAs (circRNAs) are thought to play a crucial function in controlling gene expression, according to expanding findings. However, the importance of circRNAs in the regulation of acne inflammation is unclear.
Methods
Microarray analysis has been carried out to investigate circRNAs/miRNAs/mRNAs that express abnormally in acne. RNase R digestion assay is used for confirmation of the hsa_circ_0105040 characteristic. The functional roles of hsa_circ_0105040 on inflammatory response induced by Cutibacterium acnes (C. acnes) biofilm in human primary keratinocytes were revealed by Fluorescence in situ hybridization (FISH), Reverse transcription quantitative (PCR), Western blotting analysis, Immunoprecipitation, Luciferase reporter assay, Biotin-labeled miRNA pull-down assay, RNA immunoprecipitation (RIP).
Results
We first evaluate the human circRNA expression patterns in acne tissues and find that hsa_circ_0105040 expression is considerably reduced in acne tissues. Moreover, we discover that the majority of hsa_circ_0105040 is found to be localized in the cytoplasm of primary human keratinocytes. Hsa_circ_0105040 overexpression significantly enhances the production of proinflammatory factors (interleukin-8, interleukin-6, and tumor necrosis factor-α). Mechanistic research reveals that the microRNA miR-146a binds to hsa_circ_0105040, which then actively sponges miR-146a to prevent the level of IRAK1 and TRAF6.
Conclusions
These findings point to hsa_circ_0105040 as a critical circRNA that function as "microRNA sponges" for the controlled inflammatory response in the development of acne. Our findings may provide valuable insights into the progression of acne.
... Previous studies have reported differentially expressed circRNAs from psoriatic lesions and normal skin tissues using circRNA microarray analysis, in which circ_0024028 is found to be significantly upregulated in psoriasis lesions [15]. However, circ_0024028 roles in psoriasis progression remains unclear. ...
... With the development of microarray analysis technology, many new circRNAs have been found to be abnormally expressed in psoriasis patients, which may be involved in the psoriasis process [16]. According to the results of previous analysis [15], we selected a newly discovered differentially expressed circRNA in psoriasis lesions for study. Here, circ_0024028 had been confirmed to be overexpressed in psoriasis lesions, which was consistent with previous research [15]. ...
... According to the results of previous analysis [15], we selected a newly discovered differentially expressed circRNA in psoriasis lesions for study. Here, circ_0024028 had been confirmed to be overexpressed in psoriasis lesions, which was consistent with previous research [15]. Circ_0024028 was detected to be upregulated in IL-22-induced HaCaT cells, and its knockdown restrained HaCaT cell proliferation and migration. ...
Circular RNA (circRNA) has been confirmed to participate in psoriasis process, but the role of circ_0024028 in psoriasis development is still unclear. Interleukin 22 (IL-22)-induced keratinocytes (HaCaT) were used to construct psoriasis cell models in vitro. The expression of circ_0024028, microRNA (miR)-486-3p and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time PCR. Cell function was assessed by cell counting kit 8 assay, EdU assay, transwell assay, and wound healing assay. Protein expression was examined using western blot analysis. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Exosomes were isolated from cell culture medium using ultracentrifugation and examined by transmission electron microscopy and nanoparticle tracking analysis. Circ_0024028 was highly expressed in psoriasis lesions and IL-22-induced HaCaT cells, and its silencing could inhibit IL-22-induced HaCaT cell proliferation and migration. MiR-486-3p could be sponged by circ_0024028, and its inhibitor restored the functions of circ_0024028 knockdown on IL-22-induced HaCaT cell proliferation and migration. AKT3 was targeted by miR-486-3p, and its overexpression reversed the inhibitory effect of miR-486-3p on IL-22-induced HaCaT cell proliferation and migration. AKT3 expression was positively regulated by circ_0024028, and circ_0024028/miR-486-3p/AKT3 axis could regulate the activity of AKT/mTOR pathway. Additionally, exosomes mediated the transfer of circ_0024028 in cells. Circ_0024028 might be a potential target for psoriasis treatment, which knockdown repressed IL-22-induced keratinocytes proliferation and migration through miR-486-3p/AKT3 pathway.
... Other studies, in contrast, suggest that circRNAs can be both up-and down-regulated in psoriatic lesional skin. For example, one publication reported 3016 upregulated and 1940 downregulated circRNAs in psoriatic lesions compared to healthy control samples, with many of these, such as hsa_circ_0061,012, predicted to sponge miRs that regulate T cell function and development [199]. Additional experiments by the same group demonstrated that circOAS3, a psoriatic skin induced circRNA, physically interacts with Hsp70 and regulates signaling through the JNK-MAPK, NF-κB and STAT3 pathways to enhance proliferation of keratinocytes [200]. ...
... Additional experiments by the same group demonstrated that circOAS3, a psoriatic skin induced circRNA, physically interacts with Hsp70 and regulates signaling through the JNK-MAPK, NF-κB and STAT3 pathways to enhance proliferation of keratinocytes [200]. In a further follow-up study, the authors of the original publication [199], found that one of the circRNAs upregulated in lesional skin, termed circEIF5, is an activator of the NF-κB and STAT3 pathways (through undetermined mechanisms) and regulates cellular proliferation and chemokine production [201]. Of these circRNAs, hsa_circ_0061,012 has since been independently verified by others as upregulated in psoriatic skin and to regulate proliferation of HaCaT cells, an immortalized human keratinocyte cell line, by upregulating GAB2 via sponging of miR-194-5p [202]. ...
Immune cell function is critically dependent on precise control over transcriptional output from the genome. In this respect, integration of environmental signals that regulate gene expression, specifically by transcription factors, enhancer DNA elements, genome topography and non-coding RNAs (ncRNAs), are key components. The first three have been extensively investigated. Even though non-coding RNAs represent the vast majority of cellular RNA species, this class of RNA remains historically understudied. This is partly because of a lag in technological and bioinformatic innovations specifically capable of identifying and accurately measuring their expression. Nevertheless, recent progress in this domain has enabled a profusion of publications identifying novel sub-types of ncRNAs and studies directly addressing the function of ncRNAs in human health and disease. Many ncRNAs, including circular and enhancer RNAs, have now been demonstrated to play key functions in the regulation of immune cells and to show associations with immune-mediated diseases. Some ncRNAs may function as biomarkers of disease, aiding in diagnostics and in estimating response to treatment, while others may play a direct role in the pathogenesis of disease. Importantly, some are relatively stable and are amenable to therapeutic targeting, for example through gene therapy. Here, we provide an overview of ncRNAs and review technological advances that enable their study and hold substantial promise for the future. We provide context-specific examples by examining the associations of ncRNAs with four prototypical human autoimmune diseases, specifically rheumatoid arthritis, psoriasis, inflammatory bowel disease and multiple sclerosis. We anticipate that the utility and mechanistic roles of these ncRNAs in autoimmunity will be further elucidated in the near future.
