MiR-222-3p inhibits proliferation and migration of human trophoblast by down-regulating NFATC2 in preeclampsia disease

Objectives: This study is aim to explore the possible pathological mechanism of preeclampsia, and to provide a basis for clinical prediction and preventive treatment.

Design:The miRNA and downstream target gene associated with preeclampsia were identified through bioinformatics analysis, followed by investigation of their potential roles and mechanisms using clinical samples and in vitro cell models.

Participants:30 healthy expectant mothers and 30 preeclampsia patients. HTR-8/SVneo and TEV-1 cells.

Setting:Control, Hypoxia, NC inhibitor, miR-222-3p inhibitor, Hypoxia+NC inhibitor, Hypoxia+miR-222-3p Inhibitor, Hypoxia+miR-222-3p inhibitor+si-NC, Hypoxia+miR-222-3p inhibitor+si-NFATC2.

Methods: Firstly, through literature review and database analysis, MiR-222-3p with high correlation with preeclampsia was screened as the research target. Then the downstream target genes of NFATC2 were analyzed by Starbase, Targetscan, miRDB and miRWALK databases, and the intersection analysis between these target genes and MiR-222-3p was performed to screen out NFATc2 as the downstream target gene for further study. Finally, the effects and mechanisms of MiR-222-3p and NFATC2 on human trophoblast cells were investigated using clinical samples and in vitro cell models.

Results: MiR-222-3p was highly expressed but NFATC2 was down-regulated in PE patients and hypoxic cell model, and miR-222-3p targeted and negatively regulated the expression of NFATC2. MiR-222-3p inhibitor increased cell viability, invasion and migration, and inhibited apoptosis in the hypoxic cell model, while Si-NFATC2 rescued the function of miR-222-3p inhibitor.

Limitations:The validation of specific mechanisms is still inadequate and in vivo experimental validation is lacking.

Conclusion: MiR-222-3p inhibits the proliferation and migration of preeclamptic trophoblast cells by down-regulating NFATC2.