miR-326 serves as a diagnostic biomarker in gestational diabetes mellitus and its regulatory effect on trophoblast cell viability

Abstract

Objective: To investigate the diagnostic value and mechanism of action of miR-326 in gestational diabetes mellitus (GDM).

Methods: The study population consisted of 98 GDM patients and 71 healthy pregnant women. Subjects' serum were collected early in pregnancy (10-12 weeks) for cryopreservation. Gene expression was analyzed by RT-qPCR. miR-326 was evaluated by ROC for its diagnostic value. Pearson correlation analysis was performed to calculate the relationship between miR-326 and glycemic index and TLR4. Logistic analysis resulted in risk factors for adverse pregnancy outcomes. CCK8, transwell, and flow cytometry were performed to observe changes in trophoblast function after different treatments. DLR verified the targeting relationship between genes.

Results: miR-326 is upregulated in early pregnancy serum of GDM patients and has a predictive diagnostic value for GDM. There is a positive correlation between miR-326 and glycemic indices (HbA1c, FBG, HOMA-IR) in GDM patients, which is a risk factor for inducing adverse pregnancy outcomes. miR-326 inhibitor restored the proliferation, migration, and invasion ability of high glucose-treated (HG group) cells and reduced apoptosis. TLR4 is a target gene of miR-326, and the expression of the two is negatively correlated in GDM patients. Transfection of si-TLR4 resisted the changes in trophoblast cells induced by the use of miR-326 inhibitor.

Conclusion: High levels of miR-326 are upregulated in serum of GDM patients in early pregnancy. miR-326 targeted inhibition of TLR4 causes abnormal trophoblast cell function and induces adverse pregnancy outcomes in GDM patients.

Keywords: Diagnosis; Gestational diabetes mellitus; MiR-326; TLR4; Trophoblast cells.