Upregulated lncRNA XIST drives trophoblast dysfunction through targeting miR-545-5p/POU2F1 axis in recurrent...

To investigate the specific role of long non-coding RNA (lncRNA) XIST in recurrent spontaneous abortion (RSA).

Placental tissue samples from RSA patients and healthy controls were obtained to assess expression of the XIST/miR-545-5p/POU2F1 axis. Functional assays evaluating cell proliferation, apoptosis, and invasion, as well as nuclear factor kappa B (NF-κB) pathway activity, were performed in HTR-8/Svneo trophoblasts following transfection with short hairpin RNA (shRNA), miRNA mimics, or inhibitors. The targeting relationship among these molecules was verified through dual luciferase reporter gene assays. An RSA mouse model was established to study the effects of XIST knockdown on this molecular axis and pregnancy outcomes in vivo.

In clinical RSA samples, lncRNA XIST expression was significantly upregulated. Knockdown of XIST in trophoblasts led to enhanced cell proliferation and invasion while reducing cell apoptosis. In the RSA mouse model, suppression of XIST decreased the embryonic resorption rate and improved pregnancy outcomes. Mechanistic studies revealed that XIST acts as a competing endogenous RNA that sponges miR-545-5p, thereby relieving repression of its downstream target POU2F1. Dysregulation of the XIST/miR-545-5p/POU2F1 axis contributed to trophoblast dysfunction and RSA pathogenesis through activation of the pro-inflammatory NF-κB signaling pathway.

These findings suggest that lncRNA XIST may serve as a potential prognostic marker for RSA and promote disease progression via the miR-545-5p/POU2F1 regulatory axis.