Cell-free miRNA-150-5p serves as a biomarker and regulator of PROM-related preterm labor by targeting chorionic ADAM19.

Abstract

The prediction and treatment of spontaneous preterm labor (sPTL) are critical challenges due to obscure etiology and lack of highly specific and sensitive testing methods. Here, we extended the application of noninvasive prenatal testing into the field of sPTL prediction using high-throughput small RNA sequencing to screen the potential biomarkers for sPTL in maternal peripheral blood. We found that hsa-miR-150-5p and hsa-miR-512-3p decreased in the patients affected by sPTL, compared with either term labor or term not labor patients. The change of hsa-miR-150-5p is validated using quantitative PCR with the area under the receiver operating characteristic curve (AUROC) of hsa-miR-150-5p around 0.8272. In the discovery set, hsa-miR-150-5p exhibited an AUROC of approximately 0.8508, which was validated in an independent cohort, accurately classifying preterm samples with an AUROC of 0.8010. Moreover, we showed miR-150-5p inhibited migration and invasion of chorionic cells by directly targeting a disintegrin and metalloproteinase 19 (ADAM19). The significant increase of ADAM19 in chorion from patients affected by sPTL further indicates its inverse correlationship with miR-150-5p. ADAM19 functions as a sheddase of membrane-bound TNF-α to release the TNF-α trimer into the extracellular environment, reciprocally inducing the expression of ADAM19 to form a regenerative cycle and augmenting the migration and invasion of fetal membrane cells. Remarkably, the predictive efficiency of miR-150-5p for premature rupture of membranes (PROMs)-related sPTL sharply rose to 94.21%, indicating its potential as a biomarker for preterm premature rupture of membranes (pPROMs). These findings establish miR-150-5p both as a promising noninvasive biomarker for identifying the risk of sPTL and a key regulator in pathogenesis of pPROM.NEW & NOTEWORTHY MiR-150-5p is identified as a potential noninvasive biomarker associated with sPTL and regulates chorionic cell migration, invasion, and adhesion by targeting ADAM19, a member of the ADAM family, contributing to premature rupture of fetal membranes. These findings provide new insights into the molecular mechanisms of sPTL and suggest that targeting the miR-150-5p/ADAM19 axis may offer novel therapeutic strategies.