Proteomic and miRNA Profiles of Exosomes Derived from Myometrial Tissue in Laboring Women

Deng, Wenfeng; Wang, Xiaodi; Chen, Lina; Wen, Bolun; Chen, Yunshan; Ji, Kaiyuan; Liu, Huishu

doi:10.3390/ijms232012343

Cited by 2 publications

(1 citation statement)

References 38 publications

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“…On the other hand, hsa-miR-122-5p showed a remarkable variation: it was found up-regulated in one study ( 88 ) but down-regulated in a later one ( 92 ), and this variability currently remains unexplained. Of interest, the status of hsa-miR-125b-2-3p is difficult to assess in recent publications because it cannot be determined with certainty which arms or isomiRs were measured in the studies ( 81 , 93 , 94 ). A similar question on miRNA arm usage also applies to the hsa-miR-302a or the hsa-miR-144 loci: in both cases, the downregulation of the 3p arm was detected in PE samples ( 88 , 95 ), as compared to our data on the upregulation of the 5p arm ( Table 3 ).…”

Section: Discussionmentioning

confidence: 99%

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia

Gál,

Fóthi,

Orosz

et al. 2024

Front. Immunol.

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IntroductionPreeclampsia (PE) is a severe obstetrical syndrome characterized by new-onset hypertension and proteinuria and it is often associated with fetal intrauterine growth restriction (IUGR). PE leads to long-term health complications, so early diagnosis would be crucial for timely prevention. There are multiple etiologies and subtypes of PE, and this heterogeneity has hindered accurate identification in the presymptomatic phase. Recent investigations have pointed to the potential role of small regulatory RNAs in PE, and these species, which travel in extracellular vesicles (EVs) in the circulation, have raised the possibility of non-invasive diagnostics. The aim of this study was to investigate the behavior of exosomal regulatory small RNAs in the most severe subtype of PE with IUGR.MethodsWe isolated exosomal EVs from first-trimester peripheral blood plasma samples of women who later developed preterm PE with IUGR (n=6) and gestational age-matched healthy controls (n=14). The small RNA content of EVs and their differential expression were determined by next-generation sequencing and further validated by quantitative real-time PCR. We also applied the rigorous exceRpt bioinformatics pipeline for small RNA identification, followed by target verification and Gene Ontology analysis.ResultsOverall, >2700 small RNAs were identified in all samples and, of interest, the majority belonged to the RNA interference (RNAi) pathways. Among the RNAi species, 16 differentially expressed microRNAs were up-regulated in PE, whereas up-regulated and down-regulated members were equally found among the six identified Piwi-associated RNAs. Gene ontology analysis of the predicted small RNA targets showed enrichment of genes in pathways related to immune processes involved in decidualization, placentation and embryonic development, indicating that dysregulation of the induced small RNAs is connected to the impairment of immune pathways in preeclampsia development. Finally, the subsequent validation experiments revealed that the hsa_piR_016658 piRNA is a promising biomarker candidate for preterm PE associated with IUGR.DiscussionOur rigorously designed study in a homogeneous group of patients unraveled small RNAs in circulating maternal exosomes that act on physiological pathways dysregulated in preterm PE with IUGR. Therefore, our small RNA hits are not only suitable biomarker candidates, but the revealed biological pathways may further inform us about the complex pathology of this severe PE subtype.

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