To explore the effects of microRNA-138-5p (miR-138-5p) on trophoblast invasion and angiogenesis, and to further study its regulatory impact on hypoxia-inducible factor 1α (HIF-1α) /Notch1 axis.

Human trophoblast cell line HTR-8/SVneo cultured in vitro were transfected with mimics NC (miR-NC) , miR-138-5p mimics, inhibitor negative control (inhibitor NC) , miR-138-5p inhibitor (miR-138-5p inhibitor) , pcDNA-NC (oe-NC) , pcDNA-HIF-1α (oe-HIF-1α) , miR-138-5p mimics and pcDNA-NC (miR-138-5p mimics+oe-NC) , miR-138-5p mimics and pcDNA-HIF-1α (miR-138-5p mimics +oe-HIF-1α) , respectively. After transfection, the cells were cultured for 48 h, and the proliferation was detected by MTT assay and clone formation assay; cell invasion was detected by Transwell; the apoptosis rate was detected by flow cytometry; angiogenesis was detected by tube formation test; qRT-PCR detected the expression of miR-138-5p; Western Blot detected the expressions of HIF-1α, Notch1, MMP-2, MMP-9 and VEGF; dual luciferase reporter assay verified the targeting relationship between miR-138-5p and HIF-1α.

The cell survival rate, the number of clone formations, the number of invasion and the number of tubes formed were significantly decreased after overexpression of miR-138-5p; In contrast, the apoptosis rate was significantly increased, and the protein expressions of HIF-1α, Notch1, MMP-2, MMP-9 and VEGF were significantly decreased (all P < 0.05) ; inhibition of miR-138-5p expression changed the above indicators in the opposite direction. The results of the dual-luciferase reporter gene assay showed that miR-138-5p had a targeting relationship with HIF-1α. After HIF-1α overexpression, the cell survival rate, the number of clone formation, the number of invasions and the number of tubes formed were significantly increased, the cell apoptosis rate was significantly decreased, and the expressions of Notch1, MMP-2, MMP-9 and VEGF were significantly increased (all P < 0.05) . Up-regulation of HIF-1α reversed the influence of miR-138-5p overexpression on the changes of the above indexes.

miR-138-5p may affect trophoblast cell proliferation, invasion ability and angiogenesis by targeting and negatively regulating the HIF-1α/Notch1 axis.