miR-142-3p regulates RDH13 to impair trophoblast function via regulating CDH5/LFA-1/L-SELECTIN axis: a novel mechanism and diagnostic/therapeutic for pre-eclampsia.

Background: miR-142-3p is aberrantly expressed in preeclampsia placentas, but its regulatory mechanisms in trophoblasts remain incompletely understood. Given that miRNAs exert biological effects primarily by targeting the 3'UTR of downstream genes, we prioritized potential downstream regulators of miR-142-3p to elucidate its pathogenic mechanism in preeclampsia. This study aims to elucidate how miR-142-3p modulates trophoblast functions and its clinical significance in preeclampsia pathogenesis using integrated bioinformatics and experimental approaches. Methods: Public datasets (GSE25906 and GSE10588) and miR-142-3p-related downstream target genes (predicted by the miRWalk database) were retrieved. Differentially expressed genes were identified by WGCNA and machine learning algorithms. RDH13 was identified as a candidate functional mediator of miR-142-3p based on its intersection with miR-142-3p targets, DEGs, and preeclampsia-related module genes. Clinical samples and HTR-8/Svneo cells were used for validation: miR-142-3p mimics/inhibitors and RDH13 siRNA were transfected to construct gain-of-function and loss-of-function models; co-transfection of miR-142-3p inhibitors and RDH13 siRNA was performed to verify the functional dependency. RT-qPCR and WB detected gene/protein expression. Cell apoptosis, invasion, migration, and proliferation were evaluated to clarify the functional roles of miR-142-3p and RDH13 in preeclampsia. Results: Through bioinformatics analysis, HEXB and RDH13 were identified as potential early biomarkers of preeclampsia diagnosis. Clinically, miR-142-3p was upregulated while RDH13 was downregulated in preeclamptic samples. In HTR-8/Svneo cells, miR-142-3p promoted apoptosis and inhibited invasion, migration, and proliferation, whereas RDH13 exerted opposing effects. Rescue experiments confirmed that RDH13 is a functional downstream regulator of miR-142-3p, and the regulatory roles of miR-142-3p were partially mediated by suppressing RDH13 expression-consistent with canonical miRNA-downstream gene regulatory mechanisms. Importantly, these regulatory roles of miR-142-3p were partially mediated by RDH13, which further coordinately regulated the mRNA and protein expression of CDH5, LFA-1, and L-SELECTIN across experimental groups. Conclusion: This study identifies miR-142-3p/RDH13 axis as a potential diagnostic biomarker and a promising candidate target for preeclampsia research. Functional and rescue assays confirm that miR-142-3p negatively regulates RDH13, thereby suppressing trophoblast proliferation, invasion, and migration while promoting apoptosis, revealing a novel preeclampsia-related regulatory mechanism.