THE POSSIBLE ROLE OF MIR-1910-3P, MIR-4649-3P, MIR-4296, AND MIR-210 IN THE PATHOGENESIS OF ATOPIC DERMATITIS: MAY MIR-4296 PLAY CRUCIAL ROLES IN THE DEVELOPMENT OF ATOPIC DERMATITIS?

Yıl 2022, Cilt: 29 Sayı: 3, 494 - 503, 30.09.2022

Havva Hilal Ayvaz Kuyaş Hekimler Öztürk Emrah Atay İjlal Erturan Selma Korkmaz Mehmet Yıldırım

https://doi.org/10.17343/sdutfd.1164324

Öz

Objective
Atopic dermatitis (AD) is a chronic inflammatory skin
disease with unexplained points in its pathogenesis.
Altered expressions of microRNAs (miRNA, miR) in
plasma can serve as markers that distinguish diseased
individuals from healthy controls AD. In the present
study, plasma expression levels of miR-1910-3p, miR-
4649-3p, miR-4296 and miR-210 were investigated in
AD.
Material and Method
Forty patients with AD and forty healthy control subjects
were included in the present study. Quantitative realtime
PCR was used to measure miRNAs.
Results
The mean plasma miR-4296 level was higher in the
patient group (p < 0.001). There was a significant
negative correlation between SCORAD scores and
miR-210 levels (r:-0.340, p=0.032). miR-210 levels
decreased with increasing disease severity. In logistic
regression analyses, an increase in plasma miR-4296
levels was found to be statistically significant (OR
=5.464, p<0.001). Moreover, although not significant
in other analyzes, a decrease in the miR-1910-3p was
shown statistically significant.
Conclusion
MiRNAs are crucial in the pathogenesis of AD.
Increased miR-4296 seems to be significantly better
at discriminating AD patients from healthy individuals.

Anahtar Kelimeler

Atopic dermatitis, miR-4296, miR-1910-3p, miR-210, SCORAD

ATOPİK DERMATİT PATOGENEZİNDE MİR-1910-3P, MİR-4649-3P, MİR-4296 VE MİR-210'UN OLASI ROLÜ: MİR-4296 ATOPİK DERMATİT GELİŞİMİNDE ÖNEMLİ ROL OYNAYABİLİR Mİ?

Öz

Amaç
Atopik dermatit (AD), patogenezinde açıklanamayan
noktaları olan kronik inflamatuar bir deri hastalığıdır.
Plazmadaki mikroRNA'ların (miRNA, miR) değişmiş
ekspresyonları, hastalıklı bireyleri sağlıklı kontrollerden
ayıran belirteçler olarak hizmet edebilir. Bu çalışmada,
AD’li hastalarda miR-1910-3p, miR-4649-3p,
miR-4296 ve miR-210'un plazma ekspresyon düzeyleri
araştırıldı.
Gereç ve Yöntem
Bu prospektif çalışmaya 40 AD'li hasta ve 40 sağlıklı
kontrol alındı. MiRNA'ları ölçmek için real-time PCR
kullanıldı.
Bulgular
Ortalama plazma miR-4296 düzeyi hasta grupta daha
yüksek bulundu (p < 0.001). SCORAD skorları ile
miR-210 seviyeleri arasında anlamlı bir negatif korelasyon
saptandı (r:-0.340, p=0.032). miR-210 seviyeleri
hastalık şiddeti arttıkça azalmaktaydı. Lojistik regresyon
analizinde plazma miR-4296 seviyelerinde bir
artış istatistiksel olarak anlamlı bulundu (OR =5.464,
p<0.001). Diğer analizlerde anlamlı bir farklılık bulunmasa
da miR-1910-3p seviyelerinde bir azalma da istatistiksel
olarak anlamlıydı.
Sonuç
MiRNA'lar AD patogenezinde önemli rol oynamaktadırlar.
Artan miR-4296 ekspresyon seviyeleri, AD hastalarını
sağlıklı kişilerden ayırt etmede önemli ölçüde
daha iyi görünmektedir.

Anahtar Kelimeler

Atopik dermatit, miR-4296, miR-1910-3p, miR-210, SCORAD

Kaynakça

• 1. Avena-Woods C. Overview of atopic dermatitis. The American journal of managed care 2017;23(8):115-123.
• 2. David Boothe W, Tarbox JA, Tarbox MB. Atopic Dermatitis: Pathophysiology. Advances in experimental medicine and biology 2017;1027:21-37. doi: 10.1007/978-3-319-64804-0_3.
• 3. Carroll CL, Balkrishnan R, Feldman SR, Fleischer AB Jr, Manuel JC. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatric Dermatology. 2005;22(3):192-199. doi: 10.1111/j.1525-1470.2005.22303.x.
• 4. Peng W, Novak N. Pathogenesis of atopic dermatitis. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology 2015;45(3):566-574. doi: 10.1111/cea.12495.
• 5. Makeyev EV, Maniatis T. Multilevel regulation of gene expression by microRNAs. Science 2008;319(5871):1789-1790. doi: 10.1126/science.1152326
• 6. Schneider MR. MicroRNAs as novel players in skin development, homeostasis and disease. The British journal of dermatology 2012;166(1):22-28. doi: 10.1111/j.1365-2133.2011.10568.x.
• 7. Yu X, Wang M, Li L, Zhang L, Chan MTV, et al. MicroRNAs in atopic dermatitis: A systematic review. Journal of cellular and molecular medicine, 2020; 24(11):5966-5972. doi: 10.1111/jcmm.15208
• 8. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. British journal of haematology 2008; 141(5):672-675. doi: 10.1111/j.1365-2141.2008.07077.x.
• 9. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circulation research 2010;107(6):810-817. doi: 10.1161/CIRCRESAHA.110.226357.
• 10. Rashmi R, Rao KS, Basavaraj KH. A comprehensive review of biomarkers in psoriasis. Clinical and experimental dermatology 2009; 34(6):658-663. doi: 10.1111/j.1365-2230.2009.03410.x.
• 11. Sullivan M, Silverberg NB. Current and emerging concepts in atopic dermatitis pathogenesis. Clinics in dermatology 2017; 35(4):349-353. doi: 10.1016/j.clindermatol.2017.03.006.
• 12. Klonowska J, Gleń J, Nowicki RJ, Trzeciak M. New Cytokines in the Pathogenesis of Atopic Dermatitis-New Therapeutic Targets. International journal of molecular sciences 2018;19(10):3086. doi: 10.3390/ijms19103086.
• 13. Rożalski M, Rudnicka L, Samochocki Z. MiRNA in atopic dermatitis. Postepy dermatologii i alergologii 2016;33(3):157-162. doi: 10.5114/ada.2016.60606.
• 14. Chen X, Ba Y, Ma L, Cai X, Yin Y, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases Cell research 2008, 18: 997–1006. doi: 10.1038/cr.2008.282.
• 15. Long CM, Lukomska E, Marshall NB, Nayak A, Anderson SE. Potential Inhibitory Influence of miRNA 210 on Regulatory T Cells during Epicutaneous Chemical Sensitization. Genes (Basel). 2016;8(1):9. doi:10.3390/genes8010009
• 16. Bartel S, La Grutta S, Cilluffo G, et al. Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development. Allergy. 2020;75(2):346-356. doi:10.1111/all.14008
• 17. O'Sullivan MJ, Jang JH, Panariti A, et al. Airway Epithelial Cells Drive Airway Smooth Muscle Cell Phenotype Switching to the Proliferative and Pro-inflammatory Phenotype. Front Physiol. 2021;12:687654. doi:10.3389/fphys.2021.687654.
• 18. Hanifin, JM, Rajka, G. Diagnostic features of atopic dermatitis. Acta Dermato-Venereologica 1980; 92:44-47. doi: 10.2340/00015555924447
• 19. Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31. doi: 10.1159/000247298.
• 20. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, et al. MicroRNAs in body fluids: the mix of hormones and biomarkers. Nature reviews. Clinical oncology 2011; 8: 467-477. doi: 10.1038/nrclinonc.2011.76.
• 21. Bin L, Leung DY. Genetic and epigenetic studies of atopic dermatitis. Allergy and Clinical Immunology 2016;12:52. doi: 10.1186/s13223-016-0158-5.
• 22. Bhardwaj N. MicroRNAs in atopic dermatitis: A review. Journal of translational genetics and genomics 2017;1: 15-22. doi: 10.20517/jtgg.2017.01
• 23. Sonkoly E, Wei T, Janson PC, Sääf A, Lundeberg L, et al. MicroRNAs: Novel regulators involved in the pathogenesis of psoriasis? PLoS One 2007;2: e610. doi: 10.1371/journal.pone.0000610.
• 24. Nousbeck J, McAleer MA, Hurault G, Kenny E, Harte K, et al. MicroRNA analysis of childhood atopic dermatitis reveals a role for miR‐451a*. British journal of dermatology 2021; 184: 514-523. doi: 10.1111/bjd.19254.
• 25. Lv Y, Qi R, Xu J, Di Z, Zheng H, et al. Profiling of serum and urinary microRNAs in children with atopic dermatitis. PLoS One. 2014; 22;9(12):e115448. doi: 10.1371/journal.pone.0115448.
• 26. Koga Y, Jinnin M, Ichihara A, Fujisawa A, Moriya C, et al. Analysis of expression pattern of serum microRNA levels in patients with psoriasis. Journal of dermatological science 2014;74(2):170-171. doi: 10.1016/j.jdermsci.2014.01.005.
• 27. Yan F, Meng W, Ye S, Zhang X, Mo X, et al. MicroRNA-146a as a potential regulator involved in the pathogenesis of atopic dermatitis. Molecular medicine reports 2019;20(5):4645-4653. doi: 10.3892/mmr.2019.10695.
• 28. Dissanayake E, Inoue Y, Ochiai S, Eguchi A, Nakano T, et al. Hsa-mir-144-3p expression is increased in umbilical cord serum of infants with atopic dermatitis. The Journal of allergy and clinical immunology 2019;143(1):447.e11-450.e11. doi: 10.1016/j.jaci.2018.09.024.
• 29. Gu C, Li Y, Wu J, Xu J. IFN-γ-induced microRNA-29b up-regulation contributes to keratinocyte apoptosis in atopic dermatitis through inhibiting Bcl2L2. International journal of clinical and experimental pathology 2017;10(9):10117-10126.
• 30. Herberth G, Bauer M, Gasch M, Hinz D, Röder S, et al. Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers. The Journal of allergy and clinical immunology 2014;133(2):543-550. doi: 10.1016/j.jaci.2013.06.036.
• 31. Karabacak M, Erturan İ, Hekimler Öztürk K, Ayvaz HH, Korkmaz S, et al. 'Is microrna 1910-3p (miR-1910-3p) a really distinctive marker for psoriasis?'. Turkish journal of medical sciences 2020; 28. doi: 10.3906/sag-2009-156.
• 32. Wu R, Zeng J, Yuan J, Deng X, Huang Y, et al. MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation. The Journal of clinical investigation 2018;128(6):2551-2568. doi: 10.1172/JCI97426.
• 33. Feng H, Wu R, Zhang S, Kong Y, Liu Z, et al. Topical administration of nanocarrier miRNA-210 antisense ameliorates imiquimod-induced psoriasis-like dermatitis in mice. The Journal of dermatology 2020;47(2):147-154. doi: 10.1111/1346-8138.15149.
• 34. Papadavid E, Braoudaki M, Bourdakou M, Lykoudi A, Nikolaou V, et al. Aberrant microRNA expression in tumor mycosis fungoides. Tumour biology 2016; 37(11):14667-14675. doi: 10.1007/s13277-016-5325-2.
• 35. Wang B, Mao JH, Wang BY, Wang LX, Wen HY, et al. Exosomal miR-1910-3p promotes proliferation, metastasis, and autophagy of breast cancer cells by targeting MTMR3 and activating the NF-κB signaling pathway. Cancer letters 2020;489:87-99. doi: 10.1016/j.canlet.2020.05.038.
• 36. Shen Y, Gao X, Tan W, Xu T. STAT1-mediated upregulation of lncRNA LINC00174 functions a ceRNA for miR-1910-3p to facilitate colorectal carcinoma progression through regulation of TAZ. Gene 2018;666:64-71. doi: 10.1016/j.gene.2018.05.001.
• 37. Bustos MA, Gross R, Rahimzadeh N, Cole H, Tran LT, et al. A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients. Cancers 2020;12(11):3361. doi: 10.3390/cancers12113361.
• 38. Mullany LE, Herrick JS, Wolff RK, Stevens JR, Slattery ML. Association of cigarette smoking and microRNA expression in rectal cancer: Insight into tumor phenotype. Cancer Epidemiol. 2016;45:98-107. doi:10.1016/j.canep.2016.10.011