MicroRNA-200c promotes trophoblast cell dysfunction via inhibition of PI3K/Akt signaling in unexplained recurrent spontaneous abortion.

Dysfunction in trophoblast cells is closely associated with the development of recurrent spontaneous abortion (RSA). Previous reports have indicated that microRNA (miR)-200c was upregulated in the serum of patients who have had abortions. This study aimed to investigate the regulatory effects and mechanisms of miR-200c in trophoblast cells. The human extravillous trophoblast cell line HTR-8/SVneo was either subjected to knockdown or overexpression of miR-200c, and its levels were measured using RT-qPCR. The cell behaviors of HTR-8/SVneo were assessed using CCK-8, Transwell, wound healing assays, and flow cytometry. Western blotting was used to detect the protein levels of Ki67, Bcl-2, Bax, MMP2/9, and PI3K/Akt-related markers. The findings revealed that miR-200c levels were higher in the villous tissues of URSA patients. Depletion of miR-200c impeded HTR-8/SVneo cell apoptosis and enhanced cell migration, invasiveness, and proliferation, while overexpression of miR-200c exhibited the opposite effects. The data suggested that mechanistically, miR-200c inactivated PI3K/Akt signaling in trophoblast cells. Furthermore, rescue experiments demonstrated that blocking PI3K/Akt signaling reversed the effects of miR-200c depletion on HTR-8/SVneo cell behavior. Therefore, miR-200c depletion can potentially improve trophoblast cell function by activating PI3K/Akt signaling.