lncRNA PANDAR predicts adverse pregnancy outcomes and reflects hyperglycemia-associated cellular stress in gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy associated with placental dysfunction and adverse maternal-fetal outcomes. LncRNAs have emerged as important regulators in metabolic diseases. The clinical significance and molecular mechanisms of lncRNA PANDAR in GDM remain unclear.

METHODS

117 GDM patients and 110 healthy pregnant women were enrolled. Relative expression of genes was measured by qRT-PCR. The diagnostic value of PANDAR was assessed using ROC analysis, and its association with adverse pregnancy outcomes was evaluated by logistic regression. High-glucose model was established in HTR-8/Svneo trophoblast cells to investigate the function of PANDAR. Cell apoptosis, viability, and invasion were assessed using flow cytometry, CCK-8, and Transwell assays. The regulatory relationships among molecules were validated by dual-luciferase reporter assays.

RESULTS

PANDAR expression was upregulated in GDM patients and exhibited good diagnostic performance. PANDAR levels were higher in GDM patients with adverse pregnancy outcomes. Elevated PANDAR was independently associated factor for adverse pregnancy outcomes. High glucose induced PANDAR expression and promoted trophoblast apoptosis while inhibiting cell viability and invasion, effects that were alleviated by PANDAR silencing. PANDAR functioned as a ceRNA for miR-192-5p, thereby upregulating the pro-apoptotic target BCL2L11. Rescue experiments confirmed that a PANDAR/miR-192-5p/BCL2L11 axis mediated trophoblast dysfunction under hyperglycemic conditions.

CONCLUSION

PANDAR is associated with adverse pregnancy outcomes and may reflect hyperglycemia-induced cellular responses by promoting trophoblast dysfunction via a miR-192-5p/BCL2L11 axis.