Skip to main content
Log in

Serum miR-124 up-regulation as a disease marker of toxic epidermal necrolysis

  • Investigative Report
  • Published:
European Journal of Dermatology Aims and scope

Abstract

Background

Toxic epidermal necrolysis (TEN) is a lethal complication of drugs, thus early diagnosis and treatment are important. However, there are no satisfactory clinical biomarkers of TEN.

Objectives

We investigated miR-124 and miR-214 expressions in serum and skin tissues of severe drug eruptions to evaluate the possibility of biomarkers of TEN.

Materials & Methods

microRNAs were extracted from serum and skin tissues. Serum samples were obtained from 7 TEN patients, 5 Stevens-Johnson syndrome (SJS) patients, 11 erythema multiforme (EM) minor patients and 21 healthy volunteers. Skin tissues were obtained from 4 TEN patients, 3 SJS patients, 8 EM minor patients, 3 psoriasis and 3 atopic dermatitis patients. Six control skin samples were obtained. MicroRNA concentrations were determined by PCR array and real-time PCR.

Results

The concentrations of miR-124 in sera from TEN were significantly higher than those from healthy controls. In the characteristics curve analysis of serum miR-124 for differentiating TEN patients from normal subjects, the area under curve was 0.94. The serum miR-124 concentration was strongly correlated with the erosion area and the SCORTENscale. The expression of miR-214was significantly increased in the skin of TEN.

Conclusion

The serum miR-124 concentration can be used as a disease activity marker for severe drug eruptions, reflecting the severity of keratinocyte apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abe R, Shimizu T, Shibaki A, Nakamura H, Watanabe H, Shimizu H. Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand. Am J Pathol 2003; 162: 1515–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Chung WH, Hung SI, Yang JY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med 2008; 14: 1343–50.

    Article  PubMed  CAS  Google Scholar 

  3. Sand M, Gambichler T, Sand D, et al. MicroRNAs and the skin: tiny players in the body’s largest organ. J Dermatol Sci 2009; 53: 169–75.

    Article  PubMed  CAS  Google Scholar 

  4. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–97.

    Article  PubMed  CAS  Google Scholar 

  5. Bostjancic E, Glavac D. Importance of microRNAs in skin morphogenesis and diseases. Acta Dermatovenerol Alp Pannonica Adriat 2008; 17: 95–102.

    PubMed  Google Scholar 

  6. Herrera BM, Lockstone HE, Taylor JM, et al. Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes. Diabetologia 2010; 53: 1099–109.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Cheng Y, Zhang C. MicroRNA-21 in cardiovascular disease. J Cardiovasc Transl Res 2010; 3: 251–5.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Davidson-Moncada J, Papavasiliou FN, Tam W. MicroRNAs of the immune system: roles in inflammation and cancer. Ann N Y Acad Sci 2010; 1183: 183–94.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Furer V, Greenberg JD, Attur M, et al. The role of microRNA in rheumatoid arthritis and other autoimmune diseases. Clin Immunol 2010; 136: 1–15.

    Article  PubMed  CAS  Google Scholar 

  10. Yamane K, Jinnin M, Etoh T, et al. Down-regulation of miR-124/-214 in cutaneous squamous cell carcinoma mediates abnormal cell proliferation via the induction of ERK. J Mol Med 2013; 91: 69–81.

    Article  PubMed  CAS  Google Scholar 

  11. Koukos G, Polytarchou C, Kaplan JL, et al. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology 2013; 145: 842–52.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Geng S, Zhang X, Chen J, et al. The tumor suppressor role of miR-124 in osteosarcoma. PLoS One 2014 Jun 27; 9: e91566.

  13. Shi XB, Xue L, Ma AH, et al. Tumor suppressive miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells. Oncogene 2013; 32: 4130–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Xia J, Wu Z, Yu C, et al. miR-124 inhibits cell proliferation in gastric cancer through down-regulation of SPHK1. J Pathol 2012; 227: 470–80.

    Article  PubMed  CAS  Google Scholar 

  15. Cagnol S, Chambard JC. ERK and cell death: mechanisms of ERK-induced cell death–apoptosis, autophagy and senescence. FEBS J 2010; 277: 2–21.

    Article  PubMed  CAS  Google Scholar 

  16. Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 2010; 50: 298–301.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105: 10513–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Gilad S, Meiri E, Yogev Y, et al. Serum microRNAs are promising novel biomarkers. PLoS One 2008; 3: e3148.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nakashima T, Jinnin M, Etoh T, et al. Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: its implications to therapy. PLoS One 2010; 5: e14334.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Wei CY, Ko TM, Shen CY, et al. A recent update of pharmacogenomics in drug-induced severe skin reactions. Drug Metab Pharmacokinet 2012; 27: 132–41.

    Article  PubMed  CAS  Google Scholar 

  21. Fujita Y, Yoshioka N, Abe R, et al. Rapid immunochromatographic test for serum granulysin is useful for the prediction of Stevens-Johnson syndrome and toxic epidermal necrolysis. J Am Acad Dermatol 2011; 65: 65–8.

    Article  PubMed  CAS  Google Scholar 

  22. Quaglino P, Caproni M, Antiga E, et al. Serum levels of the Th1 promoter IL-12 and the Th2 chemokine TARC are elevated in erythema multiforme and Stevens-Johnson syndrome/ toxic epidermal necrolysis and correlate with soluble Fas ligand expression. An immunoenzymatic study from the Italian Group of Immunopathology. Dermatology 2007; 214: 296–304.

    Article  PubMed  CAS  Google Scholar 

  23. Nakajima S, Watanabe H, Tohyama M, et al. High-mobility group box 1 protein (HMGB1) as a novel diagnostic tool for toxic epidermal necrolysis and Stevens-Johnson syndrome. Arch Dermatol 2011; 147: 1110–2.

    Article  PubMed  Google Scholar 

  24. Yeong EK, Lee CH, Hu FC, et al. Serum bicarbonate as a marker to predict mortality in toxic epidermal necrolysis. J Intensive Care Med 2011; 26: 250–4.

    Article  PubMed  Google Scholar 

  25. Ichihara A, Wang Z, Jinnin M, et al. Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions. J Allergy Clin Immunol 2014; 133: 1065–74.

    Article  PubMed  CAS  Google Scholar 

  26. Srivastava A, Goldberger H, Dimtchev A, et al. MicroRNA profiling in prostate cancer–the diagnostic potential of urinary miR-205 and miR-214. PLoS One 2013; 8: e76994.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Wang X, Chen J, Li F, et al. MiR-214 inhibits cell growth in hepatocellular carcinoma through suppression of β-catenin. Biochem Biophys Res Commun 2012; 428: 525–31.

    Article  PubMed  CAS  Google Scholar 

  28. Penna E, Orso F, Cimino D, et al. miR-214 coordinates melanoma progression by upregulating ALCAM through TFAP2 and miR-148b downmodulation. Cancer Res 2013; 73: 4098–111.

    Article  PubMed  CAS  Google Scholar 

  29. Farley SM, Purdy DE, Ryabinina OP, et al. Fas ligand-induced proinflammatory transcriptional responses in reconstructed human epidermis. Recruitment of the epidermal growth factor receptor and activation of MAP kinases. J Biol Chem 2008; 283: 919–28.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Asako Ichihara.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sato, S., Ichihara, A., Jinnin, M. et al. Serum miR-124 up-regulation as a disease marker of toxic epidermal necrolysis. Eur J Dermatol 25, 457–462 (2015). https://doi.org/10.1684/ejd.2015.2621

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1684/ejd.2015.2621

Key words

Navigation