Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome

OBJECTIVE: Numerous studies have confirmed the correlation of microRNAs (miRNAs) with human disease, yet few have explored the role of miR-135 in preeclampsia (PE). This study intends to discuss miR-135’s function in inflammatory response in PE by modulating proprotein convertase subtilisin/kexin-6 (PCSK6) and NLR pyrin domain containing 3 (NLRP3). METHODS: The venous blood and placental tissues were collected from PE pregnant women and 25 normal ones. The levels of miR-135, PCSK6 and NLRP3 in placenta tissues of patients were detected. Hypoxia/reoxygenation HTR-8/SVneo and HPT-8 models were established to mimic PE in vitro, and cell proliferation, colony formation, apoptosis rate, invasion, migration and inflammation were detected through gain-of and loss-of-function assays. RESULTS: MiR-135 was down-regulated, and PCSK6 and NLRP3 were up-regulated in PE patients. Up-regulating miR-135 or silencing PCSK6 strengthened colony formation ability, viability, invasion and migration ability, and weakened apoptosis and inflammation of H/R-treated HTR-8/SVneo and HPT-8 cells. Inhibition of NLRP3 negated the effects of silenced PCSK6 in H/R-treated HTR-8/SVneo and HPT-8 cells. CONCLUSIONS: Altogether, we demonstrate that up-regulated miR-135 or reduced PCSK6 attenuates inflammatory response in PE by restricting NLRP3 inflammasome, which provides novel therapy for PE treatment.