Whole transcriptome analysis and preliminary construction of ceRNA networks in obstetric antiphospholipid syndrome

Lan Zhang¹Tingting Dong^2,3Xiaoyu Ji³Pengzheng Chen^1,3*Xietong Wang^1,3*

• ¹Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
• ²Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Shandong University,, Jinan, Shandong, China
• ³Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

Background: Early diagnosis and therapeutic intervention in obstetric antiphospholipid syndrome (OAPS) are crucial for reducing adverse pregnancy outcomes and improving maternal-fetal safety. This study aimed to investigate the expression profiles of coding and non-coding RNAs in OAPS, as well as the competitive endogenous RNA (ceRNA) network involved in the pathogenesis of OAPS, thereby enhancing our comprehension of the underlying mechanisms of OAPS. Methods: Plasma samples were collected from 3 OAPS patients and 3 healthy controls. Exosomes were then isolated through differential ultracentrifugation. Comprehensive transcriptome profiling of the purified exosomes was conducted using the Illumina sequencing platform. Differential expression analysis of exosomal messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) was conducted using thresholds set at |log2(fold change) | ≥1 and P < 0.05. Subsequent bioinformatics analyses included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and establishment of an lncRNA/circRNA-miRNA-mRNA ceRNA regulatory network. Results: Exosomes were successfully isolated from both OAPS patients and healthy controls, with subsequent RNA sequencing revealing significant differences in exosomal RNA profiles. Comparative analysis identified 43 differentially expressed mRNAs (DE-mRNAs), 55 DE-lncRNAs, 19 DE-miRNAs, and 72 DE-circRNAs in OAPS-derived exosomes. Integration of these findings enabled the construction of a comprehensive ceRNA regulatory network comprising 15 miRNAs, 14 lncRNAs, 15 mRNAs, and 68 circRNAs.Functional enrichment analysis demonstrated significant associations between these differentially expressed RNAs and critical biological processes, including the AMPK, ErbB, and mTOR signaling pathways. Conclusion: This study is the first to characterize the distinct exosomal RNA expression profiles in OAPS and construct a ceRNA network related to its pathogenesis. These findings offer novel insights into the molecular mechanisms underlying OAPS and may facilitate the identification of potential biomarkers and therapeutic targets.