microRNA-520c-3p suppresses NLRP3 inflammasome activation and inflammatory cascade in preeclampsia by downregulating NLRP3

Abstract

Background: The pathogenesis of preeclampsia (PE) is suggested to be a consequence of inflammation. Previously conducted investigations on nod-like receptor pyrin domain-containing 3 (NLRP3) have shed light to its crucial role in PE. Furthermore, microRNA-520c-3p (miR-520c-3p) is observed to be implicated in inflammation. Therefore, the current study aimed to explore the role of miR-520c-3p in inflammatory cascade of PE by targeting NLRP3.

Methods: Microarray analyses were performed to screen differentially expressed genes associated with PE, and the potential relationship between miR-520c-3p and NLRP3 was analyzed. PE and normal placenta tissues were collected to determine the levels of inflammatory cytokines (IL-18, IL-33, IL-1β, IL-10, and TNF-α), miR-520c-3p and NLRP3. Hypoxic HTR8/SVneo cells were transfected with oe-NLRP3, si-NLRP3 or miR-520c-3p mimic to elucidate the functional role of NLRP3 or miR-520c-3p in the inflammatory cascade in PE, followed by the evaluation of levels of inflammatory cytokines and NLRP3 inflammasomes (NLRP3, ASC and caspase-1). Additionally, the HTR8/SVneo cell migration and invasion were evaluated.

Results: An upregulation of NLRP3, IL-18, IL-1β and TNF-α, and downregulation of miR-520c-3p, IL-33 and IL-10 were observed in PE placenta tissues. NLRP3 was found to be a target gene of miR-520c-3p. HTR8/SVneo cells after hypoxia transfected with si-NLRP3 or miR-520c-3p mimic exhibited decreased levels of inflammatory cytokines and NLRP3 inflammasomes, in addition to increased IL-10 and IL-33 levels. Moreover, enhanced migration and invasion abilities were observed in cells transfected with si-NLRP3.

Conclusion: Collectively, miR-520c-3p could potentially inhibit NLRP3 inflammasome activation and inflammatory cascade in PE by downregulating NLRP3, highlighting the potential of miR-520c-3p as a therapeutic target for PE treatment.

Keywords: Inflammatory cascade; NLRP3 inflammasomes; Preeclampsia; microRNA-520c-3p.