hsa_circRNA_092488 Exacerbates the Progression of Deep Vein Thrombosis Through the NLRP3/NF-κB Signaling Pathway

Abstract

Objective: Deep vein thrombosis (DVT) is a vascular disorder with an incidence rate of about 0.1%. Endothelial progenitor cells (EPCs) are precursor cells of endothelial cells and contribute to vascular repair and regeneration. Circular RNA (circRNA) has become a new focus of research as circRNAs are involved in various biological processes including the progression of DVT. This study explored the upregulation of hsa_circRNA_092488 in DVT patients.

Materials and methods: The expression of hsa_circRNA_092488 was evaluated in venous blood samples obtained from DVT patients (n=42) and healthy controls (n=42). Gain- and loss-of-function studies of hsa_circRNA_092488 were carried out. The expression levels of related RNAs and proteins were examined by quantitative real-time reverse-transcription polymerase chain reaction, western blotting and immunofluorescence assays. The proliferation, migration, cell cycle progression, and apoptosis of transfected cells were measured by CCK-8 assay, transwell assay, and flow cytometry. The association of hsa_circRNA_092488 and NOD-like receptor protein 3 (NLRP3) in EPCs was revealed using RNA pull-down analysis. Furthermore, the stability of NLRP3 mRNA was examined in transfected EPCs.

Results: Upregulation of hsa_circRNA_092488 was detected in blood samples from DVT patients and it had the ability to suppress the proliferation and migration of EPCs, induce cell cycle arrest from the S to the G0/G1 phase, and trigger cellular apoptosis. Furthermore, NLRP3 was identified as the potential downstream target molecule of hsa_circRNA_092488 and it could exert its regulatory functions by activating the NLRP3/nuclear factor (NF)-κB signaling pathway. Overexpression of hsa_circRNA_092488 in cells notably elevated the protein expression of caspase-1, interleukin-1β, P-NF-κB-p65/NF-κB-p65, and P-IκBα/IκBα, while knockdown of hsa_circRNA_092488 significantly reduced the levels of those proteins in EPCs.

Conclusion: hsa_circRNA_092488/NLRP3/NF-κB signaling could be a novel therapeutic candidate for the treatment of DVT.