MiR-148a-3p may contribute to flawed decidualization in recurrent implantation failure by modulating HOXC8

To evaluate whether miR-148a-3p overexpression is associated with disrupted decidualization of recurrent implantation failure (RIF).

Endometrial miRNA and mRNA expression profiles during the implantation window derived from women with and without RIF were identified using microarray and RT-qPCR. Immortalized human endometrial stromal cells (HESCs) were cultured for proliferation and in vitro decidualization assays after enhancing miR-148a-3p expression or inhibiting putative target gene homeobox C8 (HOXC8) expression. RT-qPCR, western blot, and luciferase reporter assays were used to confirm the relationship between miR-148a-3p and HOXC8 gene.

MiR-148a-3p was significantly upregulated in RIF endometrial tissues. Forced expression of miR-148a-3p notably attenuated HESC in vitro decidualization. Mechanistic studies revealed that miR-148a-3p directly bounds to the HOXC8 3' untranslated region (3'UTR) and suppressed HOXC8 expressions in both mRNA and protein levels. Further investigations demonstrated that inhibition of HOXC8 in HESCs induced similar effects on decidual process as those induced by miR-148a-3p overexpression.

Taken together, our findings suggested that elevated miR-148a-3p might account for flawed decidualization in RIF by negatively regulating HOXC8, raising the possibility that miR-148a-3p might be a novel therapeutic target in RIF.