Yang Zhenxian, Yin Xiran, Chen Cheng, Huang Shan, Li Xueqing, Yan Jianjun, Sun Qing
Department of Dermatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Laboratory of Basic Medical Science, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Inflammation. 2022 Oct;45(5):1924-1935. doi: 10.1007/s10753-022-01664-7. Epub 2022 Mar 21.
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.
银屑病是一种皮肤慢性炎症性疾病，其发病机制非常复杂。环状RNA（circRNA）在包括银屑病在内的许多疾病中发挥重要的调节作用。在本研究中，我们发现circOAS3在银屑病组织和M5诱导的角质形成细胞中表达均显著上调。在HaCaT和Ker-CT细胞中沉默circOAS3可抑制其活力，促进细胞凋亡，并使细胞周期从G1期阻滞到S期。RNA下拉和RNA免疫沉淀（RIP）分析鉴定出circOAS3与热休克同源蛋白70（Hsc70）之间存在直接相互作用。沉默circOAS3表达对Hsc70蛋白表达有负面影响，但对mRNA表达无影响。circOAS3敲低抑制了JNK/STAT3/NF-κB信号通路的激活。circOAS3或Hsc70沉默导致蛋白IL-6表达下调，从而减轻体外银屑病炎症。总之，circOAS3与Hsc70之间的相互作用通过JNK/STAT3/NF-κB信号通路介导HaCaT和Ker-CT细胞的增殖及银屑病炎症，提示circOAS3或Hsc70可能是银屑病有前景的治疗靶点。
