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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 42  |  Issue : 3  |  Page : 155-158

An insight into the value of circular RNA in psoriasis pathogenesis and its correlation with PASI score


1 Department of Dermatology and Venerology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
2 Department of Dermatology and Venerology, Faculty of Medicine, Banha University, Banha, Egypt
3 Department of Dermatology and Venerology, Faculty of Medicine, Al Sheikh Zayed General Hospital, Cairo University, Egypt

Date of Submission10-Sep-2021
Date of Acceptance17-Dec-2021
Date of Web Publication01-Sep-2022

Correspondence Address:
MD Rehab M Naguib
19 Port Saed Street, Beni Suef, Postal Code: 62511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_36_21

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  Abstract 


Background Psoriasis is a chronic hyperproliferative inflammatory disease, in which genetic and environmental factors have an important role, but the exact cause is yet unknown. Circular RNAs (circRNAs) are regulatory noncoding RNAs. They play an important role in multiple physiological and pathological processes, such as cancer, cardiovascular diseases, and neuronal diseases. Some circRNAs are involved in regulating immunity, inflammation, and cell proliferation in many types of cells.
Aim To detect the expression of circRNA (Circ0061012) in psoriatic skin of diseased patients as compared with normal control persons to investigate the possible role of circRNA in psoriasis pathogenesis and its correlation with disease severity.
Patients and methods The present study included 30 psoriatic patients and 30 healthy controls. A 4-mm punch skin biopsy was taken from patients (psoriatic lesion) and controls, and it was kept in the lysis solution for the stability of the studied parameters and was kept frozen at ‑80°Celsius till analysis of circRNA by real-time polymerase chain reaction.
Results The tissue level of circRNA (Circ0061012) was significantly higher among patients with psoriasis as compared with normal control individuals.
Conclusion circRNA could contribute to psoriasis pathogenesis through its immunomodulatory role, so it might be a therapeutic target in the future.

Keywords: circular RNAs, PASI, psoriasis, real-time polymerase chain reaction


How to cite this article:
Naguib RM, El-Rifaie AEA, El-Taweel AEA, Dahab MM. An insight into the value of circular RNA in psoriasis pathogenesis and its correlation with PASI score. Egypt J Dermatol Venerol 2022;42:155-8

How to cite this URL:
Naguib RM, El-Rifaie AEA, El-Taweel AEA, Dahab MM. An insight into the value of circular RNA in psoriasis pathogenesis and its correlation with PASI score. Egypt J Dermatol Venerol [serial online] 2022 [cited 2023 Jan 27];42:155-8. Available from: http://www.ejdv.eg.net/text.asp?2022/42/3/155/354678




  Introduction Top


Psoriasis is a chronic, immune-mediated inflammatory disease that is characterized by abnormal proliferation of the keratinocytes (KCs), which is mediated mainly by T cells in a polygenic background. The estimated global prevalence of psoriasis ranges from 2 to 4%, and it is higher in adults (0.92–8.6%) compared with that in children (0–2.1%) [1]. The incidence of psoriasis has shown a noticeable upward trend in recent years. The course of psoriasis is markedly long, and its recurrence occurs frequently, which affects the quality of life of the patients, leading to great harm toward their physical and mental health [2].

Circular RNAs (circRNAs) represent a special type of noncoding RNA molecules. CircRNAs are abundant in the eukaryotic cell cytoplasm, and they show tissue behavior and disease specificity. Comparable to linear RNAs, circRNAs are characterized by a covalently closed loop structure with neither 5’ to 3’ polarity nor a polyadenylated tail. CircRNAs are also characterized by their resistance to RNA exonuclease, which increase their stability. CircRNAs are divided into three classes: exonic circRNAs, intronic circRNAs, and exon–intron circRNAs, among which exonic circRNAs represent the vast majority. CircRNAs can regulate transcription or splicing and can interact with RNA-binding proteins [3],[4]

Some circRNAs are included in regulating immunity, inflammation, and cell proliferation in different types of cells. Because these factors contribute to psoriasis, we predicted that circRNAs also might be involved in psoriasis pathogenesis. However, nothing is known about their expression profiles and functions in psoriasis [5].

The value of our work was to assess the tissue level of circRNA (hsa_circ_0061012) in patients with psoriasis to evaluate its possible role in pathogenesis of psoriasis disease and its correlation with disease severity.


  Patients and methods Top


This case–control study included 30 patients with chronic plaque psoriasis (10 women and 20 men, with mean±SD age of 48.20±11.50 years) and 30 healthy controls (15 women and 15 men; mean±SD age of 50.40±6.6 years). Clinical data of participants are presented in [Table 1].
Table 1 Dermographic data and clinical characteristics of patients with psoriasis and controls

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The patients and controls were recruited from individuals attending the outpatient clinic of Beni-Suef University Hospitals in the period from 10 November 2019 to 2 April 2020.

Exclusion criteria included the use of any topical or systemic treatment for psoriasis in the last 3 months, patients with other types of psoriasis, or those with associated systemic or dermatological diseases. No glucocorticoids, immunosuppressant agents, and biological agents were used for 3 months before the collection of biopsies. Patients with psoriasis were not treated with ultraviolet rays for 3 months before specimen taking. No congenital or acquired autoimmune disorders and other immune-related disorders were present. No coagulopathy and other surgical diseases were present.

Patient information was collected by a dermatologist, including age, sex, affected body surface area according to the rule of nines [6], and disease severity, which was determined by Psoriasis Area and Severity Index (PASI) score .


  Results Top


The tissue circRNA(Circ0061012) expression

In the case group, mean circRNA expression was 3.70±1.49, median was 3.10, and the range was from 1.7 to 6.7. However, in the control group, mean circRNA expression was 1.01±0.04, median was 1, and the range was from 0.97 to 1.2. There was a significant difference between both groups in the level of expression (P-value <0.001), as shown in [Figure 1].
Figure 1 Circular RNA expression in both cases and control groups.

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There was a nonsignificant relation between the level of circRNA and age, disease duration, extent of psoriasis, and also PASI score of psoriatic patients. Correlations between the circRNA expression and age, disease duration, extent of psoriasis, and PASI score of psoriatic patients are shown in [Table 2].
Table 2 Correlation between circ0061012 expression and patient age, disease duration, extent of psoriasis, and PASI score of psoriatic patients

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The estimation of circRNA (Circ0061012) in the tissue was performed using the quantitative reverse transcription polymerase chain reaction (qRT PCR)

A 4-mm punch skin biopsy had been taken from patients (psoriasis lesion) and controls, and it had been kept in the lysis solution for the stability of the studied parameters and had been kept frozen at ‑80°Celsius till analysis of circRNA by qRT PCR for estimation of the tissue level of circRNA. The aim of our study was explained to each patient, and an informed consent was taken from each patient. The protocol of the study followed the ethical guidelines of the 1975 Declaration of Helsinki as reflected in the a priori approval by the Institution Human Research Committee.

RNA extraction

Total RNAs from psoriatic lesions and normal healthy skin tissues were extracted and isolated using RNeasy mini kits (PARIS TM Kits, Ambion, USA). A Nanodrop® spectrophotometer was used for measuring the actual absorbance of the isolated RNA at 260 nm, 280 nm, and 230 nm.

Reverse transcription PCR (RT-PCR)

qRT-PCR was performed using a 7900 HT Sequence Detection System (ABI, Foster City, USA) to evaluate the expression of upregulated circRNAs (hsa_circ_0061012). C-DNAs had been prepared using random primers and a ReverTra Ace qPCR Kit (Toyobo, Osaka, Japan). A power SYBR Green PCR Master Mix (Houston, Texas, USA) was used for the PCR reaction. The primer sequences of specific genes are GCTGCCATTGGAGTCCTTAT.

Statistical analysis

Data had been coded and entered using the statistical package SPSS (Statistical Package for the Social Sciences, Houston, Texas, USA) version 22. Data were presented using mean and standard deviation for quantitative data and using frequency (count) and relative frequency (percentage) for categorical data. Suitable statistical tests were used (χ2, one way analysis of variance, one sample t-test, Person’s and Spearman’s correlation) whenever needed. P-values equal to or less than 0.05 were considered statistically significant.


  Discussion Top


Psoriatic skin is characterized by inflammatory infiltration of the dermis and hyperproliferation of the epidermis. Although the etiology of psoriasis remains unknown, it is shown to be a complex, multifactorial disorder that is affected by genetic, epigenetic, and also environmental factors. T cells and immunoactive molecule-mediated inflammatory reactions play important roles. Different systemic drugs and biologic therapies have been used to treat moderate to severe psoriasis [7].

Mesenchymal stem cells are immune regulators influenced by the skin microenvironment and are involved in the psoriasis pathogenesis by the Th1-Th17/Th2 inflammatory axes that lead to the secretion of pro-inflammatory mediators. CircRNA from skin mesenchymal stem cells might affect the activity of T lymphocytes by affecting the secretion of cytokines, such as hepatocyte growth factor, interleukin (IL)-6, and IL-11 [8].

CircRNAs are involved in multiple biological processes and human disorders. They play important roles in many life processes, like aging, tissue development, insulin secretion, atherosclerotic vascular disease risk, cardiac hypertrophy, and cancer [9].

CircRNAs could contribute to the development of autoimmune disorders by regulating many biological processes, like DNA methylation, inflammatory response, and immune response. So, they can be used as potential biomarkers for the diagnosis of autoimmune disorders. It is known that psoriasis is an immune-mediated inflammatory disease that is mediated by elements of the innate and adaptive immune systems. So circRNAs could be an important regulatory factor in the development of psoriasis and so a new therapeutic target for psoriasis [10].

CircRNAs work as molecular sponges for microRNAs (miRNAs); furthermore, they affect the regulation of miRNA target gene expression. They are rich in miRNA-binding sites (miRNA response elements), and they are believed to relieve the inhibitory effect of miRNAs on their target genes, and so, increase the expression of the target genes. In this way, circRNAs act as competitive endogenous RNAs. CircRNAs play an important value in the regulation of diseases via their interaction with disease-associated miRNAs [11].

Circ_0061012 acts as a molecular sponge of miR-194-5p to elevate the expression of GRB2-associated binding protein 1 (GAB1) in HaCaT cells. GAB1 contributed to the proliferation and differentiation of epidermal cells. MiR-194 was reported to suppress cell proliferation and induce cell differentiation of KCs via grainyhead-like protein 2 [12].

Qiao et al. used qRT-PCR for the detection of 6 circRNAs in 10 psoriatic samples.

hsa_circ_0061012 was significantly upregulated (fold change 2.49) compared with normal skin samples, and the difference was statistically significant (P<0.05). Gene ontology (GO) analysis was carried out in their study. The GO analysis identified that most of the top 30 of GO enrichments are related to psoriasis, like T-cell selection, response to IL-4, and regulation of nuclear factor-kappa B import into the nucleus. These results suggested that abnormal expression of hsa_circ_0061012 might be involved in the pathogenesis of psoriasis [13].

All of the above prompted us to study the expression of circRNA (Circ0061012) in psoriasis tissues. Our study showed an upregulation of its level in psoriatic skin compared with the normal skin.

This is in agreement with the study by He et al., in which circRNA (0061012) was significantly upregulated in psoriatic lesions compared with normal skin samples. They also concluded that circ0061012 elevated the expression of Ki67 and matrix metalloproteinase 9 to promote psoriasis progression through targeting miR-194-5p/GAB1 axis. They also showed that IL-22 promotes cell proliferation, migration, and invasion of HaCaT cells through upregulating circ0061012 [14].

Another study had found a downregulation of circRNAs expression levels in the lesional relative to nonlesional skin from patients with psoriasis. This phenomenon was limited to the epidermis and cannot be explained by expression changes in factors affecting circRNA biogenesis nor by the differences in lymphocyte number in the samples. It was suggested that the downregulated circRNAome in lesional skin could be due to a passive dilution of circRNAs caused by high proliferation and turnover rates of the epidermal KCs [15].

In conclusion, circRNA (0061012) may play an important role in the pathogenesis of psoriasis, so it can be used as a therapeutic target in the future. Additional studies on a larger scale are needed to detect its detailed regulating mechanism.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 2013; 133:377–385.  Back to cited text no. 1
    
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Raychaudhuri SK, Maverakis E, Raychaudhuri SP. Diagnosis and classification of psoriasis. Autoimmun Rev 2014; 13:490–495.  Back to cited text no. 2
    
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Qu S, Zhong Y, Shang R, Zhang X, Song W, Kjems J, Li H. The emerging landscape of circular RNA in life processes. RNA Biol 2017; 14:992–999.  Back to cited text no. 3
    
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Wang M, Yu F, Wu W, Zhang Y, Chang W, Ponnusamy M et al. Circular RNAs: A novel type of non-coding RNA and their potential implications in antiviral immunity. Int J Biol Sci 2017; 13:1497–1506.  Back to cited text no. 4
    
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Han B, Chao J, Yao H. Circular RNA and its mechanisms in disease. (2018): From the bench to the clinic. Pharmacol Ther 2018; 187:31–44.  Back to cited text no. 5
    
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Kanthraj GR, Srinivas CR, Shenoi SD, Deshmukh RP, Suresh B. Comparison of computer-aided design and rule of nines methods in the evaluation of the extent of body involvement in cutaneous lesions. Arch Dermatol 1997; 133:922–923.  Back to cited text no. 6
    
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Ovejero-Benito MC, Munoz-Aceituno E, Reolid A, Saiz-Rodriguez M, Abad-Santos F. Pharmacogenetics and pharmacogenomics in moderate-to-severe psoriasis. Am J Clin Dermatol 2017; 19:209–222.  Back to cited text no. 7
    
8.
Liu R, Wang Q, Chang W, Li J, Zhang K. Characterization of the circular RNA landscape in mesenchymal stem cells from psoriatic skin lesions. Eur J Dermatol 2019; 29:29–38.  Back to cited text no. 8
    
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Chen LL, Yang L. Regulation of circRNA biogenesis (2015). RNA Biol 2015; 12:381–388.  Back to cited text no. 9
    
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Greene J, Baird AM, Brady L, Lim M, Gray SG, McDermott R, Finn SP. Circular RNAs: biogenesis, functionand role in human diseases. Front Mol Biosci 2017; 4:38.  Back to cited text no. 10
    
11.
Hansen TB et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013; 495:384–388.  Back to cited text no. 11
    
12.
Yu X, An J, Hua Y, Li Z, Yan N, Fan W et al. MicroRNA-194 regulates keratinocyte proliferation and differentiation by targeting Grainyhead-like 2 in psoriasis. Pathol Res Pract 2017; 213:89–97.  Back to cited text no. 12
    
13.
Qiao M et al. Circular RNA expression profile and analysis of their potential function in psoriasis. Cell Physiol Biochem 2018; 50:15–27.  Back to cited text no. 13
    
14.
He Q, Liu N, Hu F, Shi Q, Pi X et al. Circ_0061012 contributes to IL-22-induced proliferation, migration and invasion in keratinocytes through miR-194-5p/GAB1 axis in psoriasis. Biosci Rep 2021; 41:BSR20203130.  Back to cited text no. 14
    
15.
Moldovan LI et al. High-throughput RNA sequencing from paired lesional-and non-lesional skin reveals major alterations in the psoriasis circRNAome BMC medical genomics. BMC Med Genomics 2019; 12:1–17.  Back to cited text no. 15
    


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  [Table 1], [Table 2]



 

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