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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 42  |  Issue : 3  |  Page : 151-154

The importance of micro-RNA 224-3p in pathogenesis of NonSegmental Vitiligo


1 Department of Dermatology & Venerology, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt
2 Department of Dermatology, Beni-Suef General Hospital, Ministry of Health, Beni-Suef, Egypt
3 Department of Biochemistry, Cairo University, Cairo, Egypt

Date of Submission29-Aug-2021
Date of Acceptance07-Jan-2022
Date of Web Publication01-Sep-2022

Correspondence Address:
MD Rehab M Naguib
Department of Dermatology & Venerology, Faculty of Medicine, Beni-Suef University, Beni Suef
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_35_21

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  Abstract 


Background Vitiligo is a skin and less common hair disease characterized by a decline in melanocyte function with a prevalence of 0.5–1% in most populations. Micro-RNAs (miRNAs) are single-stranded, noncoding, short RNA molecules, they act as regulators of gene expression and play critical roles in many biological processes such as differentiation, development, and metabolism of the human-body cells.
Aim This case–control study aimed at detection of the expression of miRNA-224-3p in lesional skin of vitiligo patients as compared with normal-control persons to detect the possible role of miRNA-224-3p in the pathogenesis of vitiligo.
Patients and methods This study included 30 patients with vitiligo and 30 healthy controls. About 4-mm punch skin biopsy was taken from patients (vitiligo lesion) and controls and it was kept in lysis solution for the stability of the studied parameters and was kept frozen at −80°C till analysis of miRNA-224-3p by quantitative reverse-transcription-PCR.
Results The level of miRNA-224-3p in lesional skin of vitiligo was significantly higher as compared with normal-control persons.
Conclusion MiRNA-224-3p may play an important role in pathogenesis of vitiligo, so it can be used as a biomarker to evaluate its progression and effect of therapeutic interventions.

Keywords: micro-RNA-224-3p, PCR, vitiligo


How to cite this article:
Naguib RM, Ibrahim HA, Rashed LA, El-Rifaie AEA. The importance of micro-RNA 224-3p in pathogenesis of NonSegmental Vitiligo. Egypt J Dermatol Venerol 2022;42:151-4

How to cite this URL:
Naguib RM, Ibrahim HA, Rashed LA, El-Rifaie AEA. The importance of micro-RNA 224-3p in pathogenesis of NonSegmental Vitiligo. Egypt J Dermatol Venerol [serial online] 2022 [cited 2023 Jan 27];42:151-4. Available from: http://www.ejdv.eg.net/text.asp?2022/42/3/151/354677




  Introduction Top


Vitiligo, a depigmenting skin disease, is characterized by selective loss of melanocytes, which in turn leads to pigment dilution in the affected areas of the skin. The theories have been shown combining biochemical, immunological, and environmental events, in a genetic milieu [1].

Micro-RNAs (miRNAs) are small noncoding RNA molecules about 22 nucleotides in length that regulate gene expression by targeting mRNA. MiRNAs can bind with partial complementarity to sequences in the 3’-untranslated region of target mRNAs for the regulation of gene expression [2].

miRNAs) may play a potential role in multiple physiological and developmental processes in humans. Several studies demonstrated that miRNAs act as regulatory factors and are also involved in various aspects of the pathological process of vitiligo, like the growth, differentiation, and apoptosis of melanocytes [3].

Cellular and humoral immunity are shown to be of etiological importance in the vitiligo pathogenesis. It is noticed that some miRNAs are implicated in the immune response. These miRNAs regulate a wide range of biological processes, and have a potential value in skin T lymphocytes in the mechanism of immune disturbance in vitiligo [4].

It is most widely accepted that melanocyte destruction in vitiligo is caused by autoimmunity and oxidative-stress-mediated toxicity. There are researches that show that many cutaneous pigmentation disorders can benefit from miRNA-based therapeutic applications, including vitiligo [5].

MiRNA-224-3p was identified to be related with a decline in the expression of tumor-necrosis factor-a, keratinocyte-derived chemokine, and macrophage inflammatory protein-2, suggesting an important value for miRNA-224-3p in regulation of inflammatory cytokine production [6].

The purpose of our study is to detect the expression of miRNA-224-3p in lesional skin of vitiligo-diseased patients as compared with the normal-control persons to detect the possible role of miRNA-224-3p in the vitiligo pathogenesis.


  Patients and methods Top


This case–control study included 30 patients with nonsegmental vitiligo and 30 age-matched and sex-matched healthy controls. The patients and controls were of Fitzpatrick skin-type IV recruited from individuals attending the outpatient clinic of Beni-Suef University Hospital in the period from January 1, 2019 to June 31, 2019.

Exclusion criteria included the use of any drugs that could affect the outcome of our study as topical or systemic vitiligo treatment and the patients with systemic or other dermatologic diseases or autoimmune disorders were excluded.

Patient information was collected by one dermatologist, including age, sex, duration, type of vitiligo, and affected body-surface area according to the rule of nines [7]. Vitiligo Area Scoring Index score was calculated.

The aim of our study was explained to each patient and a written consent was taken before data collection, the protocol of the study conforms to ethical guidelines of the 1975 Declaration of Helsinki as reflected in the priori approval by Institution Human Research Committee.

Detection of micro-RNA-224-3p in tissue biopsies using quantitative reverse-transcription polymerase-chain reaction

About 4-mm punch skin biopsy had been taken from patients (vitiligo lesion) and controls and it had been kept in lysis solution for the stability of the studied parameters and had been kept frozen at −80°C till analysis of miRNA-224-3p by quantitative reverse-transcription-PCR for estimation of the level of miRNA-224-3p.

RNA extraction: RNA has been isolated using Qiagen tissue-extraction kit (Qiagen, Applied biosystems: Housten, Texas, USA) according to the instructions of the manufacturer.

cDNA synthesis: total RNA (0.5–2 µg) was used for cDNA conversion by using the high-capacity cDNA reverse-transcription kit, Fermentas, Houston, Texas, USA. Converted cDNA was then stored at approximately −20°C.

Real-time PCR using SYBR Green I: real-time qPCR amplification and analysis had been performed using Applied Biosystem with software version 3.1 (StepOne Plus, USA). Then, qPCR assay with primer sets had been optimized at annealing temperature.

Statistical analysis

Data had been coded and entered using statistical package SPSS (Statistical Package for Social Sciences), version 24 (IBM Corporation, New Orchad Road, Armonk, New York, USA). Data had been summarized using mean, SD in the quantitative data, and using frequency (count) and relative frequency (percentage) for the categorical data. The comparisons between the quantitative variables were then done using nonparametric Kruskal–Wallis and Mann–Whitney tests. The correlations between the quantitative variables had been done using the Spearman correlation coefficient. P values less than 0.05 were considered as statistically significant.


  Results Top


The sex ratio and age were not substantially different for each variable among patients with vitiligo (22 women, eight men, mean±SD age 36.2±10.5 years), and healthy controls (23 women, seven men, mean±SD age 34.2±9.61 years) .Clinical data of participants are presented in [Table 1].
Table 1 Demographic data, clinical characteristics of the vitiligo patients, and controls

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The tissue miRNA-224-3p expression.

The level of miRNA-224-3p in lesional skin of vitiligo was significantly higher as compared with normal-control persons (P<0.001), where the mean±SD were 5.44±2.40 versus 1.01±0.1 in the cases and controls, respectively ([Table 2], [Figure 1]).
Table 2 Tissue level of micro-RNA-224-3p

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Figure 1 The tissue micro-RNA-224-3p expression in cases and controls.

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The correlation analysis showed no significant correlation between miRNA-224-3p expression and age (P=0.240), extent of vitiligo (P=0.632), and duration of disease (P=0.385).


  Discussion Top


The exact pathogenesis of vitiligo is unknown, but many researches have suggested that an interplay of different factors such as genetic, neural, oxidant–antioxidant, biochemical, minerals, and autoimmune process may induce vitiligo disease [8].

Vitiligo melanocytes are more sensitive to accumulated reactive oxygen species due to the intrinsic antioxidant defects. This imbalance between pro-oxidants and antioxidant state can disrupt the homeostasis of melanocytic cells, causing the accumulation of multiple oxidized and damaged proteins or organelles, leading to destruction of melanocytes [9].

The hypersensitivity caused by oxidative stress plays important roles in the degeneration of melanocytic cells. Multiple studies found that the miRNA expression profile might be regulated by the oxidative-stress process and also can mediate the pathogenic effects of reactive oxygen species in vitiligo. This suggests that miRNAs may contribute in vitiligo pathogenesis by regulating the oxidative-stress-related gene expression in the cutaneous melanocytes [10].

MiRNAs modulate cellular proliferation, differentiation, and apoptosis, including melanocytes and immune-cell development and function. MiRNAs are shown to be unusually well preserved in serum or plasma derived from immune cells and other tissues and serve as promising biomarkers for different diseases [11].

All the above-mentioned prompted us to investigate the role of miRNA-224-3p in vitiligo pathogenesis by detection of its tissue level in skin biopsies from vitiligo patients.

Our results showed that the level of miRNA-224-3p in lesional skin of vitiligo disease was significantly higher as compared with the normal-control persons (P<0.001).

Wang et al. [12] found that the expression of miRNA-224-3p was significantly increased in the peripheral blood mononuclear cells of patients with nonsegmental vitiligo. Their analysis was associated with responses to the biological functions of the immune modulator thymosin α1, which has an important value in the mechanism of immune imbalance of vitiligo, so miRNAs could act as potential biomarkers to distinguish nonsegmental vitiligo from healthy volunteers.

Therapeutic applications based on miRNAs may be beneficial for many cutaneous pigmentation disorders like vitiligo.The therapeutic application of miRNAs includes two strategies. One strategy is suggested to inhibit pathogenic miRNAs by the use of miRNA antagonists, such as anti-miRNAs, locked-nucleic acids, or antagomiRs. These miRNA antagonists are oligonucleotides with sequences complementary to the endogenous miRNA. The second strategy, miRNA replacement, includes the reintroduction of a gene-suppressor miRNA mimic to modulate the gene expression, often resulting in a loss-of-function effect. This approach represents a second-generation RNAi-based therapy [13],[14].

Limitations of this study

The sample size of the included patients was relatively small and from a single center, which may limit the possibility that the study’s results can be generalized to the general population.


  Conclusion Top


MiRNA-224-3p can contribute to pathogenesis of vitiligo, it may be used as a biomarker to evaluate the effects of therapeutic interventions as well as a new therapeutic target in vitiligo disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rashighi M, Harris JE. Vitiligo pathogenesis and emerging treatments. Dermatol Clin 2017; 35:257–265.  Back to cited text no. 1
    
2.
Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nature Rev 2015; 16:421–433.  Back to cited text no. 2
    
3.
Mohammed GF, Gomaa AH, Al-Dhubaibi MS. Highlights in pathogenesis of vitiligo. World J Clin Cases 2015; 3:221–230.  Back to cited text no. 3
    
4.
Rebane A, Akdis CA. MicroRNAs are essential players in the regulation of inflammation. J Allergy Clin Immunol 2013; 132:15–26.  Back to cited text no. 4
    
5.
Li S, Zhu G, Yang Y, Jian Z, Guo S, Dai W et al. Oxidative stress drives CD8+ T-cell skin trafficking in patients with vitiligo through CXCL16 upregulation by activating the unfolded protein response in keratinocytes. J Allergy Clin Immunol 2017; 140:177–189.  Back to cited text no. 5
    
6.
Domingo S, Solé C, Moliné T, Ferrer B, Cortés-Hernández J. MicroRNAs in several cutaneous autoimmune diseases: psoriasis, cutaneous lupus erythematosus and atopic dermatitis. Cells 2020; 9:2656.‏  Back to cited text no. 6
    
7.
Kanthraj GR, Srinivas CR, Shenoi SD, Deshmukh RP, Suresh B. Comparison 0f 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. 7
    
8.
Bergqvist C, Ezzedine K. Vitiligo: a review. Dermatol J 2020; 236:571–592.  Back to cited text no. 8
    
9.
Jian Z, Li K, Song P, Zhu L, Cui T, Liu B et al. Impaired activation of Nrf2-ARE signaling pathway undermines H2O2-induced oxidative stress response :a possible mechanism for melanocyte degeneration in vitiligo. J Invest Dermatol 2014; 134:2221–2230.  Back to cited text no. 9
    
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Denat L, Kadekaro AL, Marrot LL, Leachman SA, Abdel-Malek ZA. Melanocytes as instigators and victims of oxidative stress. J Invest Dermatol 2014; 134:1512–1518.  Back to cited text no. 10
    
11.
Weiland M, Gao XH, Zhou L, Mi QS. Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol 2012; 9:850–859.  Back to cited text no. 11
    
12.
Wang YK, Liang J, Yang H, Dang N, Yang X, Kong Y. Differential expression analysis of miRNA in peripheral blood mononuclear cells of patients with non-segmental vitiligo. J Dermatol 2015; 42:193–197.  Back to cited text no. 12
    
13.
Maschmeyer P, Petkau G, Siracusa F, Zimmermann J, Zügel F, Kühl AA et al. Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo. J Autoimmun 2018; 89:41–52.  Back to cited text no. 13
    
14.
Gambari R, Brognara E, Spandidos DA, Fabbri E. Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: new trends in the development of miRNA therapeutic strategies in oncology (Review). Int J Oncol 2016; 49:5–32.  Back to cited text no. 14
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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