Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (<4%) Cell-Free DNA Fetal Fraction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Samples Selection
2.3. Total RNA Extraction from Plasma
2.4. NanoString nCounter Human v3 miRNA Assay
2.5. Data Analysis
3. Results
3.1. Demographic Data
3.2. Evaluation of Placenta-Specific miRNAs with Changes of Expression
3.3. Evaluation of miRNAs with Significant Changes of Expression of at Least ±1.5-Fold
3.4. Predicted Biological Processes for the Four miRNA Target Genes Selected
3.5. Selected Maternal miRNAs and Placenta-Specific Genes
3.6. Placental Proteins Encoded by miRNAs Target Genes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | Group A cfDNAff < 4% (n = 6) | Group B cfDNAff > 4% (n = 6) | p-Value * |
---|---|---|---|
GA (days) | 82.0 (72–99) | 84.5 (71–91) | >0.99 |
BMI | 22.48 (20.43–27.72) | 20.03 (17.26–25.82) | 0.065 |
Maternal age (yrs) | 33.7 (29–42) | 33.6 (26–41) | >0.99 |
Female (%) | 50 | 33.3 | 0.500 |
cfDNAff | 0.5 (0–1) | 15.5 (15–17) | - |
Neonatal weight (gr.) | 2955 (2100–3140) | 3080 (2860–3680) | 0.121 |
FGR (%) | 33.3 | 0 | <0.001 |
miRNAs | Localization |
---|---|
C19MC14 [23] | chromosome 19 encoding 46 intronic miRNAs |
C14MC11 [19] | on chromosome 14 encoding 39 miRNAs |
placenta-specific 1302 miRNA family [24] | derived from the MER53 transposon element |
as miR-371/miR-373 [25] | chromosome 19 encoding 7 miRNAs |
miR-17-92 11. [26] | chromosome 13 encoding for 6 miRNAs |
miRNA 148-152 family [27] | chromosomes 7, 12 and 17 encoding 3 miRNAs |
Placenta-Related miRNAs |
---|
hsa-let-7a-5p |
hsa-miR-210-3p |
hsa-miR-369-3p |
hsa-miR-371a-5p |
hsa-miR-512-5p |
hsa-miR-517a-3p |
hsa-miR-519a-3p |
hsa-miR-93-5p |
hsa-miR-96-5p |
hsa-miR-206 |
miRNAs | Placenta-Specific Target Genes | Gene Ontology |
---|---|---|
miR-579 | ADAMTSL4, ADM, AFF1, AFF2, AGTR1, AKR1B15, ARL14EPL, ATP6V1C2, BCAR3, C18orf54, C2orf83, CCDC102B, CLEC1A, COBLL1, COL11A1, CRYBG1, CYP19A1, DAB2, DKK1, EDNRB, EPB42, EPYC, ERVV-1, ESRRG, F13A1, F5, FAM162B, FAM46A, FBN1, FBN2, GDF6, GJB7, GM2A, GPR1, HPGDS, HSD17B2, HTR1F, HTR2B, IDO2, IGFBP1, IGSF3, IL1RAP, IL1RL1, JAM2, KATNBL1, LUM, LYPD6, MAGEA10, MB21D2, MEST, MFAP5, MUC15, NLRP10, NNAT, NRK, OLIG3, OLR1, PAPPA, PEG3, PHLDA2, PHLDB2, PKIB, PSG1, PSG2, PSG4, PSG8, RASA1, SEMA6D, SIGLEC6, SLC25A35, SPP1, STS, TBX4, TBX5, TFAP2A, TFRC, TMEM2, TWIST1, TXK, VGLL1, VGLL3, WNT2, XKRX, ZNF468 | cellular process (GO:0009987) |
metabolic process (GO:0008152) | ||
biological regulation (GO:0065007) | ||
localization (GO:0051179) | ||
multicellular organismal process (GO:0032501) | ||
response to stimulus (GO:0050896) | ||
biological adhesion (GO:0022610) | ||
developmental process (GO:0032502) | ||
immune system process (GO:0002376) | ||
cellular component organization or biogenesis (GO:0071840) | ||
reproduction (GO:0000003) | ||
cell proliferation (GO:0008283) | ||
rhythmic process (GO:0048511) | ||
biological phase (GO:0044848) | ||
nitrogen utilization (GO:0019740) | ||
miR-3144 | C2orf72, ELOVL2, HAPLN1, MORN3, P2RY1, SKP2, SLC30A2, TFPI2, TRAPPC3L, TRIM10, TRIM64B | cellular process (GO:0009987) |
metabolic process (GO:0008152) | ||
biological regulation (GO:0065007) | ||
localization (GO:0051179) | ||
multicellular organismal process (GO:0032501) | ||
response to stimulus (GO:0050896) | ||
developmental process (GO:0032502) | ||
biological adhesion (GO:0022610) | ||
locomotion (GO:0040011) | ||
pigmentation (GO:0043473) | ||
miR-6721 | AADACL3, ALPP, AOC1, APLNR, ARID3A, ASCL2, ATG9B, BIRC7, C1QTNF6, CAPN6, CD248, CDH5, CLDN19, CLDN9, COL4A2, COX4I2, CXorf67, CYP11A1, DACT2, DLX3, DUSP9, ERVFRD-1, ERVV-2, FAM129B, FSTL3, FURIN, GABRE, GDPD5, GJA5, GPR78, GRHL2, HES2, INSL4, ISM2, KLF14, LAMC3, LARGE2, LEP, LGR5, MAFK, MFSD2B, N4BP3, NOTUM, NOX5, OC90, PGF, PODNL1, PROCR, SDC1, SEMA7A, SH2D5, SLC13A4, SLC22A11, SLC43A2, SLC4A1, SLC7A4, SP6, ST3GAL4, STRA6, SYNPO, SYTL5, TIMP2, TMEM139, TNS4, TREML2, TRIM58, TRPV6, UNC13D, WNT1, WNT3A, WNT7A, ZFAT | cellular process (GO:0009987) |
metabolic process (GO:0008152) | ||
biological regulation (GO:0065007) | ||
localization (GO:0051179) | ||
multicellular organismal process (GO:0032501) | ||
response to stimulus (GO:0050896) | ||
developmental process (GO:0032502) | ||
immune system process (GO:0002376) | ||
biological adhesion (GO:0022610) | ||
cellular component organization or biogenesis (GO:0071840) | ||
reproduction (GO:0000003) | ||
cell proliferation (GO:0008283) | ||
rhythmic process (GO:0048511) | ||
biological phase (GO:0044848) | ||
signaling (GO:0023052) | ||
pigmentation (GO:0043473) | ||
multi-organism process (GO:0051704) | ||
Genes shared between miR-579 and miR-6721 | ACKR2, ADAM12, ADGRG6, APLN, ART4, CADM3, CCSAP, CD59, CLDN6, CREB3L2, CYTH3, DLK1, EGFL7, EXPH5, FHDC1, GADD45G, GCM1, GDF15, GRAMD2A, GSE1, HPGD, IGDCC3, IGF2, IGF2BP1, IL2RB, INHBA, ITIH5, KMO, LRRC15, LVRN, MBNL3, MORC4, NCMAP, PAEP, PDPN, PLAU, PRG2, QSOX1, RAI14, RGPD1, RSPO2, RXFP1, SCIN, SERPINE1, SLC2A1, SLC38A9, SLC6A2, TGM2, THSD7A, TIMP3, UCK2, ZFP42 | cellular process (GO:0009987) |
metabolic process (GO:0008152) | ||
biological regulation (GO:0065007) | ||
localization (GO:0051179) | ||
response to stimulus (GO:0050896) | ||
developmental process (GO:0032502) | ||
immune system process (GO:0002376) | ||
biological adhesion (GO:0022610) | ||
cell proliferation (GO:0008283) | ||
Genes shared between miR-579 and miR-3144 | ADAMTS20, ADAMTS5, ATP10D, CHSY1, CYSLTR2, DEPDC1B, FN1, GULP1, HGF, HMGB3, LGALS13, LIN28B, LIPG, LNPEP, MAN1A2, NECTIN3, NFE2L3, NIPAL1, PLAC8, SH3TC2, SPTLC3, TDRP, TFPI, TLR3, TUSC3 | cellular process (GO:0009987) |
metabolic process (GO:0008152) | ||
biological regulation (GO:0065007) | ||
localization (GO:0051179) | ||
multicellular organismal process (GO:0032501) | ||
response to stimulus (GO:0050896) | ||
developmental process (GO:0032502) | ||
biological adhesion (GO:0022610) | ||
immune system process (GO:0002376) | ||
reproduction (GO:0000003) | ||
cellular component organization or biogenesis (GO:0071840) | ||
Genes shared between miR-3144 and miR-6721 | ERVMER34-1, FAM89A, MFAP2, SPIRE2 | cellular process (GO:0009987) |
metabolic process (GO:0008152) | ||
biological regulation (GO:0065007) | ||
localization (GO:0051179) | ||
multicellular organismal process (GO:0032501) | ||
response to stimulus (GO:0050896) | ||
developmental process (GO:0032502) | ||
biological adhesion (GO:0022610) | ||
Genes shared Among miR-579, miR-3144 and miR-6721 | ARHGAP42, FOXO4, GUCY1A2, IGF2R, PHACTR2, PTCD2, SATB2, VAV3 | cellular process (GO:0009987) |
metabolic process (GO:0008152) | ||
biological regulation (GO:0065007) | ||
localization (GO:0051179) | ||
multicellular organismal process (GO:0032501) | ||
response to stimulus (GO:0050896) | ||
developmental process (GO:0032502) | ||
biological adhesion (GO:0022610) |
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Santoro, G.; Lapucci, C.; Giannoccaro, M.; Caporilli, S.; Rusin, M.; Seidenari, A.; Ferrari, M.; Farina, A. Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (<4%) Cell-Free DNA Fetal Fraction. Diagnostics 2021, 11, 2108. https://doi.org/10.3390/diagnostics11112108
Santoro G, Lapucci C, Giannoccaro M, Caporilli S, Rusin M, Seidenari A, Ferrari M, Farina A. Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (<4%) Cell-Free DNA Fetal Fraction. Diagnostics. 2021; 11(11):2108. https://doi.org/10.3390/diagnostics11112108
Chicago/Turabian StyleSantoro, Graziano, Cristina Lapucci, Marco Giannoccaro, Simona Caporilli, Martina Rusin, Anna Seidenari, Maurizio Ferrari, and Antonio Farina. 2021. "Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (<4%) Cell-Free DNA Fetal Fraction" Diagnostics 11, no. 11: 2108. https://doi.org/10.3390/diagnostics11112108