First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth
Abstract
:1. Introduction
2. Results
2.1. Demographic and Clinical Characteristics
2.2. Small RNA-seq Analysis
2.3. GO Analysis
2.4. qRT-PCR Assays
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Clinical Definitions
4.3. Methods
4.3.1. Total RNA and miRN Isolation
4.3.2. Small RNA-seq
4.3.3. Sequencing Data Analysis
4.3.4. miRNAs Target Gene Prediction and Gene Ontology Analysis
4.3.5. Quantitative Real-Time Polymerase Chain Reaction Verification
4.3.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | Controls (n = 34) | sPTD Cases (n = 34) | p-Value |
---|---|---|---|
Maternal age (y) Median (min–max) | 31.00 (24.80–38.80) | 30.65 (24.80–38.20) | 0.898 |
Pre-pregnancy BMI (kg/m2) Median (min–max) | 25.95 (22.00–31.20) | 24.65 (20.90–31.90) | 0.028 |
Cigarette smoker
| 12 22 | 8 26 | 0.40 |
Mode of conception
| 28 (82.4%) 6 (17.6%) | 26 (76.4%) 8 (23.6%) | 0.750 |
Parity
| 17 (50%) 17 (50%) | 14 (41.2%) 20 (58.8%) | 0.616 |
Previous PTD
| 32 (94.1%) 2 (5.88%) | 27 (79.4%) 7 (20.58%) | 0.104 |
Mode of Delivery
| 29 (85.2%) 5 (14.7%) | 22 (64.7%) 12 (35.2%) | 0.075 |
Neonatal Gender
| 18 (52.95%) 16 (47.05%) | 16 (47.05%) 18 (52.95%) | 0.95 |
Down-Regulated miRNAs | |||
---|---|---|---|
GO.ID | Term | p-Value | Genes |
GO:0048585 | Negative regulation of response to stimulus | 0.000 | RGS4//IL10//NDFIP1//GPRC5A//STAP1//MTMR4//TMEM127//BRCA1//GREM2//HGS//STK38//FAP//TPT1 |
GO:0014854 | Response to inactivity | 0.001 | MTMR4//IL10 |
GO:1900119 | Positive regulation of execution phase of apoptosis | 0.001 | FAP//BOK |
GO:0009968 | Negative regulation of signal transduction | 0.001 | RGS4//GPRC5A//IL10//MTMR4//TMEM127//BRCA1//GREM2//HGS//STK38//STAP1//TPT1 |
GO:0043032 | Positive regulation of macrophage activation | 0.001 | STAP1//IL10 |
GO:0010324 | Membrane invagination | 0.001 | ABCA1//STAP1//HGS |
GO:1900120 | Regulation of receptor binding | 0.002 | GREM2//IL10 |
GO:0010648 | Negative regulation of cell communication | 0.002 | RGS4//GPRC5A//IL10//MTMR4//TMEM127//BRCA1//GREM2//HGS//STK38//STAP1//TPT1 |
GO:0023057 | Negative regulation of signaling | 0.002 | RGS4//GPRC5A//IL10//MTMR4//TMEM127//BRCA1//GREM2//HGS//STK38//STAP1//TPT1 |
GO:0070230 | Positive regulation of lymphocyte apoptotic process | 0.002 | IL10//PDCD1 |
Up-Regulated miRNAs | |||
GO.ID | Term | p-Value | GENES |
GO:0006397 | mRNA processing | 0.008 | RAVER2//LUC7L3//ALKBH5 |
GO:0045625 | Regulation of T-helper 1 cell differentiation | 0.009 | SOCS5 |
GO:0071071 | Regulation of phospholipid biosynthetic process | 0.009 | HTR2A |
GO:0002829 | Negative regulation of type 2 immune response | 0.010 | SOCS5 |
GO:0006054 | N-acetylneuraminate metabolic process | 0.010 | CMAS |
GO:0007175 | Negative regulation of epidermal growth factor-activated receptor activity | 0.010 | SOCS5 |
GO:0035970 | Peptidyl-threonine dephosphorylation | 0.010 | PPM1E |
GO:0042118 | Endothelial cell activation | 0.010 | SOCS5 |
GO:0045623 | Negative regulation of T-helper cell differentiation | 0.010 | SOCS5 |
GO:0043371 | Negative regulation of CD4-positive, alpha-beta T cell differentiation | 0.011 | SOCS5 |
Pathway ID | Definition | p-Value | FDR | Enricment Score | Gene Ratio | Genes |
---|---|---|---|---|---|---|
hsa04660 | T cell receptor signaling | 0.0021 | 0.658 | 2.671681 | 0.16 | IL10//PDCD1//TEC |
hsa03440 | Homologous recombination | 0.0046 | 0.713 | 2.335566 | 0.11 | BRCA1//FAM175A |
hsa04380 | Osteoclast differentiation | 0.0425 | 1 | 1.37106 | 0.11 | SIRPA//TEC |
Univariate Analysis | |||
---|---|---|---|
Covariant | OR a | 95% CI b | p-Value c |
miR-23b-5p | 1.057 | 0.943–1.184 | 0.343 |
miR-125a-3p | 0.654 | 0.490–0.872 | 0.004 |
Previous PTD | 7.154 | 0.809–63.30 | 0.077 |
Smoking | 0.535 | 0.176–1.624 | 0.269 |
Maternal pre-pregnancy BMI | 0.808 | 0.650–1.003 | 0.053 |
Mode of conception Natural IVF | 1.00 1.512 | 0.425–5.384 | 0.523 |
Fetal gender Male Female | 1.00 1.319 | 0.470–3.703 | 0.600 |
Maternal age | 1.016 | 0.885–1.167 | 0.819 |
Multivariate analysis d | |||
Covariant | OR a | 95% CI b | p-Value c |
miR125a-3p | 0.491 | 0.295–0.817 | 0.006 |
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Mavreli, D.; Theodora, M.; Avgeris, M.; Papantoniou, N.; Antsaklis, P.; Daskalakis, G.; Kolialexi, A. First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth. Int. J. Mol. Sci. 2022, 23, 14972. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314972
Mavreli D, Theodora M, Avgeris M, Papantoniou N, Antsaklis P, Daskalakis G, Kolialexi A. First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth. International Journal of Molecular Sciences. 2022; 23(23):14972. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314972
Chicago/Turabian StyleMavreli, Danai, Mariana Theodora, Margaritis Avgeris, Nikolas Papantoniou, Panagiotis Antsaklis, George Daskalakis, and Aggeliki Kolialexi. 2022. "First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth" International Journal of Molecular Sciences 23, no. 23: 14972. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314972