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CircOAS3 Regulates Keratinocyte Proliferation and Psoriatic Inflammation by Interacting with Hsc70 via the JNK/STAT3/NF-κB Signaling Pathway

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Abstract

Psoriasis is a chronic inflammatory disease of the skin with a very complex pathogenesis. Circular RNAs (circRNAs) play important regulatory roles in many diseases, including psoriasis. In this study, we found that circOAS3 expression was significantly upregulated in both psoriatic tissues and M5-induced keratinocytes. Silencing circOAS3 in HaCaT and Ker-CT cells inhibited their viability, promoted apoptosis, and blocked the cell cycle from the G1 to the S phase. RNA pull-down and RNA immunoprecipitation (RIP) analyses led to the identification of a direct interaction between circOAS3 and heat shock cognate protein 70 (Hsc70). Silencing circOAS3 expression negatively influenced Hsc70 protein expression but not mRNA expression. circOAS3 knockdown suppressed the activation of the JNK/STAT3/NF-κB signaling pathway. circOAS3 or Hsc70 silencing led to downregulated protein IL-6 expression, thus reducing psoriatic inflammation in vitro. In conclusion, the interaction between circOAS3 and Hsc70 mediates the proliferation and psoriatic inflammation of HaCaT and Ker-CT cells through the JNK/STAT3/NF-κB signaling pathway, suggesting that circOAS3 or Hsc70 may be a promising therapeutic target for psoriasis.

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AVAILABILITY OF DATA AND MATERIALS

The original data are maintained by the first author and the corresponding author, and all experimental raw data can be obtained from either of these authors when necessary.

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ACKNOWLEDGEMENTS

The authors thank all the members of the laboratory for their help.

Funding

This work was supported by the National Major Science and Technology Projects of China (Grant No. 2017YFA0104604) and the National Natural Science Foundation of China (Grant Nos. 81972937 and 82003344).

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Authors and Affiliations

  1. Department of Dermatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Zhenxian Yang, Xiran Yin, Shan Huang, Xueqing Li & Qing Sun

  2. Department of Dermatology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Cheng Chen, Jianjun Yan & Qing Sun

  3. Laboratory of Basic Medical Science, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Zhenxian Yang, Xiran Yin, Cheng Chen, Shan Huang, Xueqing Li & Jianjun Yan

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  1. Zhenxian Yang
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  2. Xiran Yin
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  3. Cheng Chen
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Contributions

Zhenxian Yang contributed to the conception and design of the work and the analysis and interpretation of the data and drafted the manuscript. Xiran Yin and Cheng Chen contributed to the design of the work and the analysis and interpretation of the data. Shan Huang, Xueqing Li, and Jianjun Yan contributed to the acquisition and interpretation of the data. Qing Sun contributed to the conception and design of the work. All authors read and approved the final manuscript.

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Correspondence to Qing Sun.

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Ethics Approval and Consent to Participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by Qilu Hospital of Shandong University, which issued an affidavit of approval of animal ethics and welfare (No. KYLL-2017(KS)-152).

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The authors declare no competing interests.

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Yang, Z., Yin, X., Chen, C. et al. CircOAS3 Regulates Keratinocyte Proliferation and Psoriatic Inflammation by Interacting with Hsc70 via the JNK/STAT3/NF-κB Signaling Pathway. Inflammation 45, 1924–1935 (2022). https://doi.org/10.1007/s10753-022-01664-7

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  • DOI: https://doi.org/10.1007/s10753-022-01664-7

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