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Screening and analysis of plasma differential lncRNA/mRNA in early pregnancy of preeclampsia
Xin Zhang1,2,3, Ning Yang4, Jie Lu1,5
1Clinical School of Cardiovascular Disease, Tianjin Medical University, Tianjin, 300457, China.
Insights
Early pregnancy long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression is altered in preeclampsia (PE). These changes correlate with disease pathways and may offer novel biomarkers for early PE detection.
Area of Science:
- Reproductive biology
- Molecular genetics
- Biomarker discovery
Background:
- Preeclampsia (PE) is a serious pregnancy complication.
- Early diagnosis of PE remains a challenge.
- Identifying molecular signatures in early pregnancy is crucial for timely intervention.
Purpose of the Study:
- To characterize long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in early pregnancy plasma of preeclampsia (PE) patients.
- To identify key signaling pathways and biological functions associated with dysregulated transcripts in PE.
- To evaluate the potential of these transcripts as early diagnostic biomarkers for PE.
Main Methods:
- Analysis of plasma samples from eight PE patients and eight controls using transcriptome sequencing (Illumina HiSeq 4000).
- Identification of differentially expressed lncRNAs and mRNAs (|fold change (FC)| ≥ 2, P ≤ 0.05).
- Functional enrichment analyses (Gene Ontology, KEGG) and lncRNA-mRNA coexpression network construction.
Main Results:
- Identified 361 dysregulated lncRNAs and 3,798 dysregulated mRNAs in PE plasma.
- Top transcripts include ENST00000440816 (lncRNA) and TEX35 (mRNA).
- Enrichment in inflammatory response, cell adhesion, PI3K-AKT, NF-κB, and mTOR signaling pathways; associations with oxidative stress.
Conclusions:
- Early pregnancy plasma lncRNAs and mRNAs are significantly dysregulated in PE, correlating with pathogenic pathways.
- Specific lncRNAs (|log2FC| ≥ 5) and mRNAs (|log2FC| ≥ 6) show potential as novel biomarkers for early PE prediction.
- These findings support the use of transcriptomic analysis for early PE diagnosis and therapeutic target identification.
Objectives:
This study aimed to characterise the expression profiles of long non-coding RNA (lncRNA) and messenger RNA (mRNA) in plasma samples from individuals with preeclampsia (PE) during early pregnancy (7-14 weeks of gestation). We sought to identify key signalling pathways and biological functions linked to these transcripts and evaluate their potential for early PE diagnosis and therapeutic intervention.
Methods:
From January to June 2019, we analysed frozen plasma samples from eight PE patients and eight normotensive pregnant women matched for gestational age. Transcriptome sequencing was performed using the Illumina HiSeq 4000 platform. Differentially expressed lncRNAs and mRNAs were identified with thresholds of |fold change (FC)| ≥ 2 and P ≤ 0.05. Functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]) were conducted to elucidate associated pathways, and a lncRNA-mRNA coexpression network was constructed to explore regulatory interactions.
Results:
We identified 361 significantly dysregulated lncRNAs (171 up- and 190 down-regulated) and 3,798 mRNAs (3,320 up- and 478 down-regulated). Top dysregulated transcripts included ENST00000440816 (lncRNA, log2FC = +175.29) and TEX35 (mRNA, log2FC = +8.70). Gene Ontology analysis revealed enrichment in inflammatory response, cell adhesion, and transferase activity, while Kyoto Encyclopedia of Genes and Genomes pathways implicated phosphoinositide 3-kinase-protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mechanistic target of rapamycin (mTOR) signalling. Coexpression networks highlighted strong associations between dysregulated transcripts and oxidative stress/inflammatory processes.
Conclusion:
Early-pregnancy plasma lncRNAs and mRNAs are markedly dysregulated in PE and correlate with pathogenic pathways. Notably, lncRNAs with |log2FC| ≥ 5 and mRNAs with |log2FC| ≥ 6 may serve as novel biomarkers for early PE prediction.
