Inhibition of microRNA-149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway.

Aim: Recently, microRNA-149 (miR-149) has been indicated to act as an oncogene or a tumor suppressor in various malignant tumors, while its inner mechanisms in recurrent miscarriage (RM) are still in infancy. Therein, this study intends to decode the mechanism of miR-149 in RM.

Methods: miR-149 and RUNX2 expression in the chorionic tissues of normal pregnant women and RM patients were first examined, and the correlation between miR-149 and RUNX2 was analyzed. Subsequently, miR-149 was upregulated in HTR-8 cells or downregulated in BEWO cells, and then the changes in biological functions of trophoblasts in RM were detected. Furthermore, the expression of PTEN/Akt signaling pathway-related factors in trophoblasts was detected by western blot analysis.

Results: miR-149 expression was increased while RUNX2 expression was suppressed in RM patients, and miR-149 was negatively correlated with RUNX2. Overexpressed miR-149 induced cell apoptosis and inhibited cell activity, while reduced miR-149 in trophoblasts contributed to opposite experimental results. Moreover, miR-149 promoted the expression of PTEN and inhibited Akt phosphorylation by targeting RUNX2, thereby inhibiting trophoblast activity and promoting their apoptosis.

Conclusion: Our study demonstrates that miR-149 knockdown halted the RM development through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway.