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

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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.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

The present study was supported by the Hubei Provincial Health Commission Fund (Grant No. WJ2019F048).

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Author notes

  1. Yong Fang and Cailing E have contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Renmin Hospital, Hubei University of Medicine, No. 39 Chaoyang Middle Road, Maojian District, Shiyan City, 442100, Hubei Province, China

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

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  1. Yong Fang
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  2. Cailing E
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  3. Shixing Wu
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  4. Zudong Meng
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Correspondence to Rongying Wang.

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Fang, Y., E, C., Wu, S. et al. Circ-IGF1R plays a significant role in psoriasis via regulation of a miR-194-5p/CDK1 axis. Cytotechnology 73, 775–785 (2021). https://doi.org/10.1007/s10616-021-00496-x

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  • DOI: https://doi.org/10.1007/s10616-021-00496-x

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