Upregulation of microRNA-3687 promotes gestational diabetes mellitus by inhibiting follistatin-like 3

Abstract

Objectives: Pregnancy-related medical complications such as gestational diabetes mellitus (GDM) are common and associated with several obstetric and neonatal problems. There is growing evidence that microRNAs (miRNAs) are essential players in the pathophysiology of GDM. This study aimed to assess how particular miRNAs and the genes they target are expressed in GDM.

Methods: A GDM cell model was created using BeWo cells cultured in hyperglycemic (HG) conditions (25 mM glucose). Low-glucose (LG) conditions (5.5 mM glucose) were used for the BeWo cells in the control group. Differentially expressed genes (DEGs) in BeWo cells were identified by high-throughput sequencing and their levels verified in placental samples from GDM patients and controls using RT-PCR. Furthermore, the target genes of the DEGs were verified using dual-luciferase reporter assays.

Results: High-throughput sequencing revealed 220 DEGs in BeWo cells. Among these, miR-3687 was significantly upregulated, while follistatin-like 3 (FSTL3) was downregulated in BeWo cells under HG conditions. The high-throughput sequencing results were corroborated by RT-PCR, which showed that placental samples from GDM patients had significantly lower levels of FSTL3 expression and substantially higher amounts of miR-3687 expression compared to control samples. FSTL3 was established as a direct target of miR-3687 as shown by dual-luciferase reporter assays.

Conclusions: The increase of miR-3687 might facilitate the onset and advancement of GDM by suppressing FSTL3. This discovery offered a new perspective on the molecular underpinnings of GDM and indicated possible targets for therapeutic intervention.

Keywords: follistatin-like 3 (FSTL3); gestational diabetes mellitus (GDM); miR-3687; microRNAs.