Gestational diabetes mellitus (GDM) is a common pregnancy complication with a high incidence in women; however, its pathophysiology remains unknown. Our previous study suggested that the circCHD2/miR-33b-3p/ULK1 axis may be involved in GDM pathogenesis. However, the mechanism through which circCHD2 regulates GDM development requires further investigation. We found that high-glucose (HG, 25 mmol/L) significantly induced the expression of circCHD2, increased autophagy and apoptosis, and decreased cell viability in human placental trophoblast HTR-8/SVneo cells. In contrast, the downregulation of circCHD2 significantly attenuated the effects of HG on HTR-8/SVneo cells. MiR-33b-3p downregulated in the placenta of GDM patients was reduced by HG and detected as a target of circCHD2 using bioinformatics analysis, a dual-luciferase reporter assay, and qRT-PCR assay. Further studies showed that the inhibition of miR-33b-3p significantly blocked the effects of circCHD2 downregulation on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. ULK1 is a target of miR-33b-3p, based on bioinformatics analysis, a dual-luciferase reporter assay, qRT-PCR assay, and Western blot analysis. Compared to miR-33b-3p, ULK1 is upregulated in the placenta of GDM patients. ULK1 overexpression notably blocked the effects of miR-33b-3p mimics on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. These findings suggested that circCHD2 acts as an autophagy promoter via the miR-33b-3p/ULK1 axis to induce apoptosis in HTR-8/SVneo cells, suggesting that circCHD2 is a potential diagnostic and therapeutic target for GDM.
Keyphrases
- cell cycle arrest
- induced apoptosis
- endoplasmic reticulum stress
- cell death
- oxidative stress
- signaling pathway
- pi k akt
- high glucose
- end stage renal disease
- newly diagnosed
- endothelial cells
- high throughput
- pregnant women
- chronic kidney disease
- ejection fraction
- metabolic syndrome
- cell proliferation
- magnetic resonance
- bioinformatics analysis
- fluorescent probe
- transcription factor
- magnetic resonance imaging
- poor prognosis
- climate change
- diabetic rats
- south africa
- preterm birth
- long non coding rna
- drug induced
- binding protein