Circ-IGF1R plays a significant role in psoriasis via regulation of a miR-194-5p/CDK1 axis View Full Text


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Article Info

DATE

2021-09-30

AUTHORS

Yong Fang, Cailing E, Shixing Wu, Zudong Meng, Guifang Qin, Rongying Wang

ABSTRACT

Psoriasis is a skin disorder that is classed as an autoimmune disease. It is characterized by excessive proliferation, abnormal migration and differentiation of keratinocytes, as well as inflammatory cell infiltration. Circular RNAs (circRNAs/circ) have been reported to play an important role in several aspects of psoriasis. Thus in the present study, the role of circ-insulin-like growth factor 1 receptor (circ-IGF1R) in the development of psoriasis was assessed, and the involvement of microRNA (miR)-194-5p was also investigated as its expression was downregulated in psoriasis. StarBase analysis and dual luciferase reporter assays confirmed the interaction between circ-IGF1R with miR-194-5p. The increased expression of circ-IGF1R and decreased expression of miR-194-5p were further confirmed by reverse transcription-quantitative polymerase chain reaction in interleukin (IL-22)-stimulated HaCaT cells. The increased proliferation, migration and invasion, as well as decreased apoptosis, caspase 3 activity and cleaved-caspase 3/caspase 3 ratio were observed in IL-22-stimulated HaCaT cells. Conversely, transfection of circ-IGF1R-small interfering (si)RNA resulted in significantly increased expression of miR-194-5p with or without stimulation of IL-22 in HaCaT cells, and also overcame the effects of the miR-194-5p inhibitor. Additionally, transfection of circ-IGF1R-siRNA inhibited cell proliferation, migration and invasion, which were reversed by transfection of a miR-194-5p inhibitor. Similarly, circ-IGF1R-siRNA promoted apoptosis, caspase 3 activity and the cleaved-caspase 3/caspase 3 ratio, which were reversed by miR-194-5p inhibitor. These results showed that circ-IGF1R could affect the proliferation, apoptosis, migration and invasion of IL-22-stimulated HaCaT cells by regulating the expression of miR-194-5p. Based on TargetScan prediction and dual luciferase reporter assays, it was shown that cyclin-dependent kinase (CDK)1 was targeted by miR-194-5p. Additionally, the expression of CDK1 was upregulated following stimulation with IL-22 in HaCaT cells at the mRNA and protein levels. Transfection of miR-194-5p mimic or miR-194-5p inhibitor negatively regulated CDK1 expression in the IL-22 induced HaCaT cells. In conclusion, circ-IGF1R-siRNA could inhibit the cell proliferation, migration and invasion, and induce apoptosis by regulating the miR-194-5p/CDK1 axis. circ-IGF1R may thus serve as a potential treatment target for psoriasis. More... »

PAGES

775-785

References to SciGraph publications

  • 2007-07-31. Immunopathogenesis of Psoriasis in CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
  • 2020-11-19. miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression in BIOCHEMICAL GENETICS
  • 1983-05. Immunocompetent cells in psoriasis in ARCHIVES OF DERMATOLOGICAL RESEARCH
  • 2016-02. microRNAs in Psoriasis in JOURNAL OF INVESTIGATIVE DERMATOLOGY
  • 2016-03-30. The Inflammatory Response in Psoriasis: a Comprehensive Review in CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
  • 2020-05-24. The new function of circRNA: translation in CLINICAL AND TRANSLATIONAL ONCOLOGY
  • 2019-08-08. The biogenesis, biology and characterization of circular RNAs in NATURE REVIEWS GENETICS
  • 2019-01. Characterisation of the circular RNA landscape in mesenchymal stem cells from psoriatic skin lesions in EUROPEAN JOURNAL OF DERMATOLOGY
  • 2019-12-01. Possible role of hsa-miR-194-5p, via regulation of HS3ST2, in the pathogenesis of atopic dermatitis in children in EUROPEAN JOURNAL OF DERMATOLOGY
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    DOI

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    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34776628


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