MELTF-AS1 Regulates DUSP5 and Trophoblast Function via EZH2 to Inhibit Preeclampsia

Objective: To explore the mechanism by which lncRNA MELTF-AS1 binds EZH2 to downregulate target gene DUSP5, thereby promoting trophoblast function and inhibiting the occurrence of preeclampsia (PE). Methods: Bioinformatic re-analysis of dataset GSE183466 identified the lncRNA MELTF-AS1 as a key dysregulated transcript in preeclampsia. Transcriptome sequencing after MELTF-AS1 knockdown identified DUSP5. CCK-8, colony formation, and Transwell assays evaluated effects on HTR-8/SVneo cell proliferation/invasion. Nuclear-cytoplasmic separation localizedthe action site of MELTF-AS1. RIP-qPCR/CHIP-qPCR clarified binding mechanisms of MELTF-AS1/DUSP5, with reduced uterine perfusion pressure mice verifying conclusions. Results: In this study, Bioinformatic analysis identified that MELTF-AS1 was significantly downregulated in the PE group. Transcriptome sequencing after MELTF-AS1 knockdown showed that DUSP5 was significantly upregulated. MELTF-AS1 enhanced cell proliferation/invasion, while DUSP5 inhibited them. Nuclear-cytoplasmic separation assay revealed that MELTF-AS1 was expressed in both the nucleus and cytoplasm. Further RIP-qPCR and CHIP-qPCR showed that MELTF-AS1 could bind to EZH2, promoting the enrichment of EZH2 at the DUSP5 promoter region and increasing the level of H3K27me3 modification, thereby reducing DUSP5 transcriptional level. Conclusion: This study reveals the regulatory mechanism mediated by MELTF-AS1, and the MELTF-AS1/DUSP5 regulatory pathway may provide new predictive and therapeutic intervention strategies for PE.