Hsa_circRNA_092488 Exacerbates the Progression of Deep Vein Thrombosis Through the NLRP3/NFkB Signaling Pathway.

Abstract

Objective: Deep vein thrombosis (DVT) is a type of vascular disorder and the incidence is around 0.1%. Endothelial progenitor cells (EPCs) are precursor cells of endothelial cells and contribute to vascular repair and regeneration. CircRNAs become a new research hotspot as they are involved in various biological processes including the progression of DVT.

Material 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. Expression of related RNA and protein was examined by qRT-PCR, western blotting and immunofluorescence assays. The proliferation, migration, cell cycle and apoptosis of transfected cells were measured by CCK-8, Transwell assay as well as Flow cytometry. The association of hsa_circRNA_092488 and NLRP3 in EPCs was unrevealed using RNA pull-down analysis. Furthermore, stabilities of NLRP3 mRNA were examined in transfected EPCs.

Results: In this study, up-regulation of hsa_circRNA_092488 was detected in DVT samples, which could suppress the proliferation and migration of EPCs, induce cell cycle arrest from S to G0/G1 phase and trigger cell apoptosis. Furthermore, NLRP3 was identified as the potential downstream molecule of hsa_circRNA_092488, and it could exert its regulatory functions through activating the NLRP3/NF-kB signaling. Overexpressed hsa_circRNA_092488 in the cell notably elevated the protein expression of caspase-1, IL-1b, P-NF-κB-p65/NF-κB-p65 and P-IκBa/IκBa; and vice versa, knockdown of hsa_circRNA_092488 significantly reduced the levels of these related proteins in EPCs.

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