TABLE 3.
Top Gene Ontology (GO) pathways of predicted target genes regulated by miRNAs showing gestational dynamics.
| Gene Ontology |
Pathway genes | Target genes in enrichment querya |
Enrichment | ||
| Term | Name | % | n | % | P-valueb |
| Target genes for miRNAs significantly UPregulated in transition from first to second trimesterc | |||||
| GO:0005515 | Protein binding | 11.5% | 991 | 90.9% | 7.5 × 10–76 |
| GO:0048522 | Positive regulation of cellular process | 19.9% | 728 | 66.8% | 4.0 × 10–160 |
| GO:0005829 | Cytosol | 12.7% | 525 | 48.2% | 1.5 × 10–25 |
| GO:0003730 | mRNA 3′-UTR binding | 32.7% | 18 | 1.7% | 9.9 × 10–4 |
| GO:0051881 | Regulation of mitochondrial membrane potential | 28.3% | 17 | 1.6% | 2.0 × 10–2 |
| GO:0010494 | Cytoplasmic stress granule | 33.3% | 15 | 1.4% | 7.2 × 10–3 |
| GO:0030212 | Hyaluronan metabolic process | 48.1% | 13 | 1.2% | 2.2 × 10–4 |
| GO:0061980 | Regulatory RNA binding | 41.9% | 13 | 1.2% | 1.6 × 10–3 |
| GO:0010586 | miRNA metabolic process | 40.7% | 11 | 1.0% | 1.7 × 10–2 |
| GO:0030020 | Extracellular matrix structural constituent conferring tensile strength | 43.5% | 10 | 0.9% | 2.2 × 10–2 |
| Target genes for miRNAs significantly DOWNregulated in transition from first to second trimesterc | |||||
| GO:0031974 | Membrane-enclosed lumen | 8.0% | 353 | 54.4% | 9.7 × 10–23 |
| GO:0070887 | Cellular response to chemical stimulus | 15.6% | 343 | 52.9% | 7.1 × 10–97 |
| GO:0072659 | Protein localization to plasma membrane | 13.1% | 26 | 4.0% | 2.6 × 10–2 |
| GO:0019867 | Outer membrane | 13.5% | 24 | 3.7% | 3.6 × 10–2 |
| GO:0051480 | Regulation of cytosolic calcium ion concentration | 13.9% | 23 | 3.5% | 3.4 × 10–2 |
| GO:0051924 | Regulation of calcium ion transport | 15.6% | 22 | 3.4% | 7.5 × 10–3 |
| GO:0008361 | Regulation of cell size | 16.5% | 21 | 3.2% | 4.8 × 10–3 |
| GO:0016605 | PML body | 22.6% | 19 | 2.9% | 9.1 × 10–5 |
| GO:0035296 | Regulation of tube diameter | 19.0% | 15 | 2.3% | 2.6 × 10–2 |
| GO:0006305 | DNA alkylation | 24.4% | 11 | 1.7% | 3.3 × 10–2 |
| Target genes for miRNAs significantly UPregulated in transition from second trimester to termc | |||||
| GO:0005515 | Protein binding | 10.6% | 909 | 90.1% | 7.1 × 10–64 |
| GO:0048518 | Positive regulation of biological process | 17.0% | 694 | 68.8% | 1.1 × 10–133 |
| GO:0005829 | Cytosol | 11.8% | 488 | 48.4% | 5.8 × 10–24 |
| GO:0046914 | Transition metal ion binding | 14.5% | 109 | 10.8% | 7.8 × 10–7 |
| GO:2000060 | Positive regulation of ubiquitin-dependent protein catabolic process | 22.7% | 20 | 2.0% | 4.0 × 10–2 |
| GO:0000045 | Autophagosome assembly | 23.2% | 19 | 1.9% | 4.8 × 10–2 |
| GO:0010494 | Cytoplasmic stress granule | 31.1% | 14 | 1.4% | 1.7 × 10–2 |
| GO:0030020 | Extracellular matrix structural constituent conferring tensile strength | 43.5% | 10 | 1.0% | 1.2 × 10–2 |
| GO:1902751 | Positive regulation of cell cycle G2/M phase transition | 43.5% | 10 | 1.0% | 1.2 × 10–2 |
| GO:0070242 | Thymocyte apoptotic process | 52.9% | 9 | 0.9% | 4.6 × 10–3 |
| Target genes for miRNAs significantly DOWNregulated in transition from second trimester to termc | |||||
| GO:0005515 | Protein binding | 8.0% | 684 | 91.3% | 1.9 × 10–52 |
| GO:0048518 | Positive regulation of biological process | 13.2% | 537 | 71.7% | 3.1 × 10–113 |
| GO:0043233 | Organelle lumen | 9.0% | 395 | 52.7% | 3.5 × 10–22 |
| GO:0019898 | Extrinsic component of membrane | 14.5% | 29 | 3.9% | 2.1 × 10–2 |
| GO:0007204 | Positive regulation of cytosolic calcium ion concentration | 16.1% | 25 | 3.3% | 1.4 × 10–2 |
| GO:0003730 | mRNA 3′-UTR binding | 25.5% | 14 | 1.9% | 8.4 × 10–3 |
| GO:0036092 | Phosphatidylinositol-3-phosphate biosynthetic process | 39.4% | 13 | 1.7% | 6.1 × 10–5 |
| GO:0030301 | Cholesterol transport | 25.0% | 13 | 1.7% | 2.4 × 10–2 |
| GO:0061980 | Regulatory RNA binding | 38.7% | 12 | 1.6% | 2.7 × 10–4 |
| GO:0045987 | Positive regulation of smooth muscle contraction | 42.1% | 8 | 1.1% | 2.0 × 10–2 |
aTop 10 pathways per each gene list analysis are shown, sorted by the highest percentage of representation among the query genes. Full results of in silico functional enrichment analyses of gene lists are in Supplementary Tables 12, 13. bP-value corrected for multiple testing by g: SCS method (Reimand et al., 2007). cQuery lists of miRNA target gene were extracted from the miRTarBase database (Huang et al., 2020).