PMID- 36524356
OWN - NLM
STAT- MEDLINE
DCOM- 20221223
LR  - 20230113
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 27
IP  - 2
DP  - 2023 Feb
TI  - WNT5A, beta‑catenin and SUFU expression patterns, and the significance of microRNA 
      deregulation in placentas with intrauterine growth restriction.
LID - 28 [pii]
LID - 10.3892/mmr.2022.12914 [doi]
AB  - Placental insufficiency is a common cause of intrauterine growth restriction 
      (IUGR). It affects ~10% of pregnancies and increases fetal and neonatal morbidity 
      and mortality. Although Wnt and Hh pathways are crucial for embryonic development 
      and placentation, their role in the pathology of IUGR is still not sufficiently 
      explored. The present study analyzed the expression of positive regulators of the 
      Wnt pathway, WNT5A and beta‑catenin, and the expression of the Hh pathway negative 
      regulator suppressor of fused (SUFU). Immunohistochemical and reverse 
      transcription‑quantitative PCR (RT‑qPCR) assays were performed on 34 IUGR and 18 
      placental tissue samples from physiologic singleton‑term pregnancies. Epigenetic 
      mechanisms of SUFU gene regulation were also investigated by methylation‑specific 
      PCR analysis of its promoter and RT‑qPCR analysis of miR‑214‑3p and miR‑378a‑5p 
      expression. WNT5A protein expression was higher in endothelial cells of placental 
      villi from IUGR compared with control tissues. That was also the case for 
      beta‑catenin protein expression in trophoblasts and endothelial cells and SUFU 
      protein expression in trophoblasts from IUGR placentas. The SUFU gene promoter 
      remained unmethylated in all tissue samples, while miR‑214‑3p and miR‑378a‑5p 
      were downregulated in IUGR. The present results suggested altered Wnt and Hh 
      signaling in IUGR. DNA methylation did not appear to be a mechanism of SUFU 
      regulation in the pathogenesis of IUGR, but its expression could be regulated by 
      miRNA targeting.
FAU - Sola, Ida Marija
AU  - Sola IM
AD  - Department of Obstetrics and Gynecology, University Hospital Sestre Milosrdnice, 
      10000 Zagreb, Croatia.
FAU - Karin-Kujundzic, Valentina
AU  - Karin-Kujundzic V
AD  - Department of Biology, University of Zagreb, 10000 Zagreb, Croatia.
FAU - Paic, Frane
AU  - Paic F
AD  - Department of Biology, University of Zagreb, 10000 Zagreb, Croatia.
FAU - Lijovic, Lada
AU  - Lijovic L
AD  - Department of Anesthesiology and Critical Care, General Hospital Fra Mihovil 
      Sucic, 80101 Livno, Bosnia and Herzegovina, 10000 Zagreb, Croatia.
FAU - Glibo, Mislav
AU  - Glibo M
AD  - Department of Biology, University of Zagreb, 10000 Zagreb, Croatia.
FAU - Serman, Nikola
AU  - Serman N
AD  - Zagreb Emergency Medicine Service; 6Department of Pathology, School of Medicine, 
      University of Zagreb, 10000 Zagreb, Croatia.
FAU - Duic, Tihana
AU  - Duic T
AD  - Department of Biology, University of Zagreb, 10000 Zagreb, Croatia.
FAU - Skrtic, Anita
AU  - Skrtic A
AD  - Centre of Excellence in Reproductive and Regenerative Medicine, School of 
      Medicine, University of Zagreb, 10000 Zagreb, Croatia.
FAU - Kuna, Krunoslav
AU  - Kuna K
AD  - Department of Obstetrics and Gynecology, University Hospital Sestre Milosrdnice, 
      10000 Zagreb, Croatia.
FAU - Vranic, Semir
AU  - Vranic S
AD  - College of Medicine, QU Health, Qatar University, 2713 Doha, Qatar.
FAU - Serman, Ljiljana
AU  - Serman L
AD  - Department of Biology, University of Zagreb, 10000 Zagreb, Croatia.
LA  - eng
PT  - Journal Article
DEP - 20221216
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (beta Catenin)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN214 microRNA, human)
RN  - 0 (Repressor Proteins)
RN  - 0 (SUFU protein, human)
RN  - 0 (Wnt-5a Protein)
RN  - 0 (WNT5A protein, human)
RN  - 0 (MIRN378 microRNA, human)
SB  - IM
MH  - Female
MH  - Humans
MH  - Infant, Newborn
MH  - Pregnancy
MH  - *beta Catenin/genetics/metabolism
MH  - Endothelial Cells/metabolism
MH  - *Fetal Growth Retardation/genetics/pathology
MH  - *MicroRNAs/genetics/metabolism
MH  - Placenta/metabolism/pathology
MH  - Repressor Proteins/genetics/metabolism
MH  - *Wnt-5a Protein/genetics/metabolism
PMC - PMC9813565
OTO - NOTNLM
OT  - DNA methylation
OT  - Hh signaling pathway
OT  - WNT5A
OT  - Wnt signaling pathway
OT  - intrauterine growth restriction
OT  - microRNA 214
OT  - microRNA 378
OT  - placenta
OT  - suppressor of fused
OT  - beta‑catenin
COIS- The authors declare that they have no competing interests.
EDAT- 2022/12/17 06:00
MHDA- 2022/12/20 06:00
PMCR- 2022/12/13
CRDT- 2022/12/16 03:42
PHST- 2022/07/07 00:00 [received]
PHST- 2022/10/05 00:00 [accepted]
PHST- 2022/12/16 03:42 [entrez]
PHST- 2022/12/17 06:00 [pubmed]
PHST- 2022/12/20 06:00 [medline]
PHST- 2022/12/13 00:00 [pmc-release]
AID - 28 [pii]
AID - MMR-27-02-12914 [pii]
AID - 10.3892/mmr.2022.12914 [doi]
PST - ppublish
SO  - Mol Med Rep. 2023 Feb;27(2):28. doi: 10.3892/mmr.2022.12914. Epub 2022 Dec 16.