Psoriasis is a chronic in ammatory disease of the skin with highly complex pathogenesis. CircRNAs play an important regulatory role in plenty of diseases as well as psoriasis. In this study, we identi ed that circOAS3 was signi cantly upregulated in both psoriatic tissues and M5-induced keratinocytes. Silencing circOAS3 in HaCaT and Ker-CT cells inhibited cell viability, promoted apoptosis, and blocked the cell cycle from G1 to S phase. RNA-pulldown and RNA immunoprecipitation (RIP) analysis identi ed the direct combination between circOAS3 and Heat shock cognate protein 70 (Hsc70). Silencing circOAS3 negatively in uences the Hsc70 in protein level rather than mRNA level. In mechanism, circOAS3 knockdown suppressed the activation of JNK/STAT3/NF-κB signaling pathways and blocked the nuclear accumulation of Hsc70 as well as phosphorylated STAT3/JNK/NF-κB as a result. Phenotypically, circOAS3 or Hsc70 silencing down-regulated the protein levels of IL-6 thus reducing psoriatic in ammation in vitro. In conclusion, interaction between circOAS3 and Hsc70 modulates the proliferation and psoriatic in ammation of HaCaT and Ker-CT cells through the JNK/STAT3/NF-κB signaling pathways, suggesting that circOAS3 or Hsc70 may be a promising therapeutic target for psoriasis. stem cells, including the expression of keratin 5 and p63. When grown in 3D organotypic culture, the epidermis formed by Ker-CT cells is pretty similar to that formed by primary keratinocytes under the same conditions [15]. Research showed Ker-CT cells are well suitable for studies on epidermal cell adhesion and Pemphigus pathomechanisms [17]. Here we make an attempt to use Ker-CT cells as a model of psoriasis as well as HaCaT cells.In this study, we determined circOAS3 was signi cantly up-regulated in psoriatic tissues and psoriatic cell lines. We further found that Hsc70 may function as the RNA binding protein (RBP) of circOAS3 to promote disease progression via JNK/STAT3/NF-κB signaling pathways. Therefore, circOAS3 or Hsc70 can serve as a biomarker for prognosis prediction and as a potential therapeutic target in treatment.
Methods
Patients and tissue samples collectionA total of 7 psoriatic samples were collected from patients with vulgaris psoriasis from Qilu Hospital of Shandong University. The patient did not receive systemic and local treatment within 3 months. All of them had typical psoriasis vulgaris clinical characteristics. 10 normal tissues were collected from healthy volunteers. Healthy subjects had no family history of psoriasis or any other autoimmune diseases.This study was approved by the Ethics Committee of Shandong University, Qilu Hospital (Jinan, China) and written informed consent was obtained from all patients. circRNAs microarray Affymetrix GeneChip Human Gene 2.0 ST Array (Invitrogen) was used for circRNAs expression pro ling. Cells were cryopulverized and homogenized using the Biopulverizer™ (Biospec) and Mini-Bead-Beater16 (Biospec), respectively. The homogenized samples were separated. RNA was precipitated, washed with 75% etha...