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Possible role of hsa-miR-194-5p, via regulation of HS3ST2, in the pathogenesis of atopic dermatitis in children

  • Investigative Report
  • Published:
European Journal of Dermatology

Abstract

Background

Atopic dermatitis (AD) is a prevalent inflammatory skin disease. Ample evidence has shown that non-coding RNAs play important roles in the progression of AD, however, the function of plasma microRNAs in AD is poorly understood.

Objectives

To identify key plasma microRNAs and explore their potential roles in AD.

Materials and Methods

Plasma microRNAs from five children with AD and five control children were sequenced by microRNA sequencing (miRNA-seq) and five differentially expressed microRNAs were verified by RT-qPCR in 30 AD and 15 control children. The most differentially expressed microRNA, hsa-miR-194-5p, was selected for further analysis. Human epidermal keratinocytes were subjected to RNA sequencing following over-expression of hsa-miR-194-5p, and down-regulated genes were detected by RT-qPCR. The diagnostic potential of hsa-miR-194-5p in AD was evaluated based on receiver operating characteristic (ROC) curve analysis. Further hsa-miR-194-5p-regulated expression and gene-hsa-miR-194-5p interactions were evaluated by western blotting and luciferase assays, respectively.

Results

We identified 40 differentially expressed microRNAs, 26 up-regulated and 14 down-regulated, in children with AD compared with controls. Among the five verified plasma microRNAs, the most significant change was down-regulated hsa-miR-194-5p, which was shown to potentially serve as a biomarker for AD based on ROC analysis. Twenty-two down-regulated genes were observed following hsa-miR-194-5p over-expression, which were significantly associated with keratinocyte differentiation and establishment of the skin barrier. Moreover, HS3ST2 protein expression was down-regulated following over-expression of hsa-miR-194-5p, and the 3′-UTR of HS3ST2 was shown to bind to hsa-miR-194-5p.

Conclusion

Hsa-miR-194-5p might be involved in the pathogenesis of AD by regulating HS3ST2 expression.

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References

  1. Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387: 1109–22.

    Article  PubMed  Google Scholar 

  2. Halkjaer LB, Loland L, Buchvald FF, et al. Development of atopic dermatitis during the first 3 years of life: the Copenhagen prospective study on asthma in childhood cohort study in high-risk children. Arch Dermatol 2006; 142: 5614.

    Article  Google Scholar 

  3. Abrams EM, Sicherer S. Cutaneous sensitization to peanut in children with atopic dermatitis: a window to prevention of peanut allergy. JAMA Dermatol 2019; 155: 13–4.

    Article  PubMed  Google Scholar 

  4. Tollefson MM, Bruckner AL. Section On D. Atopic dermatitis: skin-directed management. Pediatrics 2014; 134: e1735–44.

    Article  PubMed  Google Scholar 

  5. Li HM, Xiao YJ, Min ZS, Tan C. Identification and interaction analysis of key genes and microRNAs in atopic dermatitis by bioinformatics analysis. Clin Exp Dermatol 2019; 44: 25744.

    Google Scholar 

  6. Holgate ST, Polosa R. Treatment strategies for allergy and asthma. Nat Rev Immunol 2008; 8: 218–30.

    Article  CAS  PubMed  Google Scholar 

  7. Tam HH, Calderon MA, Manikam L, et al. Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review. Allergy 2016; 71: 1345–56.

    Article  CAS  PubMed  Google Scholar 

  8. Macfarlane LA, Murphy PR. MicroRNA: Biogenesis, function and role in cancer. Curr Genomics 2010; 11: 537–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Makeyev EV, Maniatis T. Multilevel regulation of gene expression by microRNAs. Science 2008; 319: 1789–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lu TX, Rothenberg ME. Diagnostic, functional, and therapeutic roles of microRNA in allergic diseases. J Allergy Clin Immunol 2013; 132: 3–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen XF, Zhang LJ, Zhang J, et al. MiR-151a is involved in the pathogenesis of atopic dermatitis by regulating interleukin-12 receptor beta2. Exp Dermatol 2018; 27: 427–32.

    Article  CAS  PubMed  Google Scholar 

  12. Sonkoly E, Janson P, Majuri ML, et al. MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4. J Allergy Clin Immunol 2010; 126: 581–9, e1-20.

    Article  CAS  PubMed  Google Scholar 

  13. Zeng YP, Nguyen GH, Jin HZ. MicroRNA-143 inhibits IL-13-induced dysregulation of the epidermal barrier-related proteins in skin keratinocytes via targeting to IL-13R alpha1. Mol Cell Biochem 2016; 416: 63–70.

    Article  CAS  PubMed  Google Scholar 

  14. Rebane A, Runnel T, Aab A, et al. MicroRNA-146a alleviates chronic skin inflammation in atopic dermatitis through suppression of innate immune responses in keratinocytes. J Allergy Clin Immunol 2014; 134: 836–47, e11.

    Article  CAS  PubMed  Google Scholar 

  15. Leng N, Dawson JA, Thomson JA, et al. EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments. Biolnformatics 2013; 29: 1035–43.

    Article  CAS  Google Scholar 

  16. Kruger J, Rehmsmeier M. RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res 2006; 34: W451–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Xu G, Wu J, Zhou L, et al. Characterization of the small RNA transcriptomes of androgen dependent and independent prostate cancer cell line by deep sequencing. PLoS One 2010; 5: e15519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang J, Wang Y, Zhen P, et al. Genome-wide analysis of miRNA signature differentially expressed in doxorubicin-resistant and parental human hepatocellular carcinoma cell lines. PLoS One 2013; 8: e54111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rozalski M, Rudnicka L, Samochocki Z. MiRNA in atopic dermatitis. Postepy Dermatol Alergol 2016; 33: 157–62.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Cardona ID, Cho SH, Leung DY. Role of bacterial superantigens in atopic dermatitis: implications for future therapeutic strategies. Am J Clin Dermatol 2006; 7: 273–9.

    Article  PubMed  Google Scholar 

  21. Suárez-Fariñas M, Tintle SJ, Shemer A, et al. Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol 2011; 127: 954–64, e1-4.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lv Y, Qi R, Xu J, et al. Profiling of serum and urinary microRNAs in children with atopic dermatitis. PLoS One 2014; 9: e115448.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T. New microRNAs from mouse and human. RNA 2003; 9: 175–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wu TH, Pan CY, Lin MC, Hsieh JC, Hui CF, Chen JY. In vivo screening of zebrafish microRNA responses to bacterial infection and their possible roles in regulating immune response genes after lipopolysaccharide stimulation. Fish Physiol Biochem 2012; 38: 1299–310.

    Article  CAS  PubMed  Google Scholar 

  25. Tian H, Liu C, Zou X, Wu W, Zhang C, Yuan D. MiRNA-194 regulates palmitic acid-induced Toll-like receptor 4 inflammatory responses in THP-1 cells. Nutrients 2015; 7: 3483–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kong L, Sun M, Jiang Z, Li L, Lu B. MicroRNA-194 inhibits lipopolysaccharide-induced inflammatory response in nucleus pulposus cells of the intervertebral disc by targeting TNF receptor-associated factor 6 (TRAF6). Med Sci Monit 2018; 24: 3056–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yu X, An J, Hua Y, et al. MicroRNA-194 regulates keratinocyte proliferation and differentiation by targeting Grainyhead-like 2 in psoriasis. Pathol Res Pract 2017; 213: 89–97.

    Article  CAS  PubMed  Google Scholar 

  28. Dusílková N, Bašová P, Polívka J, et al. Plasma miR-155, miR-203, and miR-205 are biomarkers for monitoring of primary cutaneous T-cell lymphomas. Int J Mol Sci 2017; 18: 2136.

    Article  PubMed Central  CAS  Google Scholar 

  29. Vanhie A, Peterse OD, Beckers D, et al. Plasma miRNAs as biomarkers for endometriosis. Hum Reprod 2019; 34: 1650–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Specjalski K, Jassem E. MicroRNAs: potential biomarkers and targets of therapy in allergic diseases? Arch Immunol Ther Exp (Warsz) 2019; 67: 213–23.

    Article  CAS  Google Scholar 

  31. Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013; 368: 1685–94.

    Article  CAS  PubMed  Google Scholar 

  32. Wu A, Chen H, Xu C, et al. miR-203a is involved in HBx-induced inflammation by targeting Rap1a. Exp Cell Res 2016; 349: 191–7.

    Article  CAS  PubMed  Google Scholar 

  33. Kyriakis JM, Avruch J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev 2012; 92: 689–737.

    Article  CAS  PubMed  Google Scholar 

  34. Tohgasaki T, Ozawa N, Yoshino T, et al. Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes. Int J Cosmet Sci 2018; 40: 178–86.

    Article  CAS  PubMed  Google Scholar 

  35. Lee E, Lee SY, Yoon JS, Jung S, Hong SJ. Mold exposure affects the development of atopic dermatitis in infants with skin barrier dysfunction. Ann Allergy Asthma Immunol 2018; 121: 372–4, e1.

    Article  PubMed  Google Scholar 

  36. Vijaya Kumar A, Salem Gassar E, Spillmann D, et al. HS3ST2 modulates breast cancer cell invasiveness via MAP kinase- and Tcf4 (Tcf7l2)-dependent regulation of protease and cadherin expression. Int J Cancer 2014; 135: 2579–92.

    Article  CAS  PubMed  Google Scholar 

  37. Suhovskih AV, Domanitskaya NV, Tsidulko AY, Prudnikova TY, Kashuba VI, Grigorieva EV. Tissue-specificity of heparan sulfate biosynthetic machinery in cancer. Cell Adh Migr 2015; 9: 452–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang L. Glycosaminoglycan (GAG) biosynthesis and GAG-binding proteins. Prog Mol Biol Transl Sci 2010; 93: 1–17.

    Article  CAS  PubMed  Google Scholar 

  39. Huang RL, Chan HJ, Chen LY, et al. Methylomics profiling reveals epigenetically silenced HS3ST2 sensitize IL6 signaling and confers poor prognosis of ovarian cancer. Can Res 2017; 77: 681.

    Google Scholar 

  40. Tilg H, Dinarello CA, Mier JW. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 1997; 18: 428–32.

    Article  CAS  PubMed  Google Scholar 

  41. Navarini AA, French LE, Hofbauer GF. Interrupting IL-6-receptor signaling improves atopic dermatitis but associates with bacterial superinfection. J Allergy Clin Immunol 2011; 128: 1128–30.

    Article  CAS  PubMed  Google Scholar 

  42. Pellerin L, Henry J, Hsu CY, et al. Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin. J Allergy Clin Immunol 2013; 131: 1094–102.

    Article  CAS  PubMed  Google Scholar 

  43. Kim BE, Leung DY, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol 2008; 126: 332–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements and disclosures

Acknowledgements: We would like to thank our colleagues in the institute of Shanghai Skin Disease Hospital. This work was funded by the National Natural Science Foundation of China (No. 81602744). Conflicts of interest: none.

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Authors and Affiliations

  1. Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China

    Li Meng, Min Li, Zhiqin Gao, Hongjin Ren, Jian Chen, Xiaoping Liu, Qing Cai, Long Jiang, Xiangyu Ren, Qian Yu, Jia Chen & Lianjuan Yang

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  1. Li Meng
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  2. Min Li
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  3. Zhiqin Gao
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Correspondence to Jian Chen or Lianjuan Yang.

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Meng, L., Li, M., Gao, Z. et al. Possible role of hsa-miR-194-5p, via regulation of HS3ST2, in the pathogenesis of atopic dermatitis in children. Eur J Dermatol 29, 603–613 (2019). https://doi.org/10.1684/ejd.2019.3676

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