Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia

Hayder, Heyam; Shan, Yanan; Chen, Yan; O’Brien, Jacob A.; Peng, Chun

doi:10.3389/fcell.2022.995462

Cited by 9 publications

(2 citation statements)

References 370 publications

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“…Notably, this expression pattern is opposite to miR-218-5p, which spikes in second trimester, during the active spiral artery remodeling period (19). Thus, the temporal expression pattern of i17/18 is consistent with a negative regulatory role of these isoforms in the enEVT pathway because the main function of enEVT is to help transform the spiral artery (18,53). IHC revealed that NLRC5 isoforms were present in all subtypes of trophoblasts, suggesting that these proteins may also regulate STB differentiation and/or functions.…”

Section: Discussionmentioning

confidence: 80%

Truncated NLRC5 isoforms in human placenta: expression, regulation by miR-218-5p, and function in trophoblasts

Shan,

O’Brian,

Nadeem

et al. 2024

Preprint

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A key event during placenta development is the differentiation of trophoblast progenitor cells into the invasive extravillous trophoblasts (EVTs) that migrate into the uterus. A subset of EVTs further acquire endothelial-like properties and differentiate into endovascular EVTs (enEVTs) to remodel the maternal spiral arteries. Proper EVT differentiation, migration/invasion, and spiral artery remodeling are critical for a healthy pregnancy. We recently reported that hsa-miR-218-5p promotes EVT/enEVT differentiation and spiral artery remodeling. In this study, we further investigated the mechanisms underlying the actions of miR-218-5p in human trophoblasts and identified NLRC5 as a target gene of miR-218-5p. Interestingly, we found that the human placenta expresses predominantly two transcript variants (v22 and v23) of the human NLRC5 gene, which encode two truncated protein isoforms 17 and 18 (i17 and i18). The expression of these isoforms declined during the active period of spiral artery remodeling. In vitro and ex vivo studies revealed that overexpression of v22 or v23 suppressed, while silencing of v22/23 enhanced, cell migration, invasion, endothelial-like network formation, and enEVT marker expression, as well as the EVT outgrowth of first trimester placental explants. Mechanistically, i17 and i18 regulated trophoblast activity by inhibiting NFκB. These findings suggest that NLRC5 isoforms are important regulators of EVT/enEVT differentiation and/or function, highlighting a novel miR-218-5p/NLRC5/NFκB signaling axis in placental development.

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Section: Discussionmentioning

confidence: 80%

Truncated NLRC5 isoforms in human placenta: expression, regulation by miR-218-5p, and function in trophoblasts

Shan,

O’Brian,

Nadeem

et al. 2024

Preprint

Self Cite

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“…Expression of this protein is spatially and temporally regulated during embryonic development [49]. The overactivity of miR-135a affects the inhibition of normal trophoblast invasion of the uterine vasculature during the first trimester of pregnancy [57, 82, 84]. This prevents the formation of a low-resistance and the wide-flow oxygen exchange system between the mother and the fetus.…”

Section: Resultsmentioning

confidence: 99%

The role of miRNA molecules in the miscarriage process

Omeljaniuk

Laudański

Miltyk

2023

Biology of Reproduction

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The etiology and pathogenesis of miscarriage, which is the most common pregnancy complication, have not been fully elucidated. There is a constant search for new screening biomarkers that would allow for the early diagnosis of disorders associated with pregnancy pathology. The profiling of miRNA expression is a promising research area, which can help establish the predictive factors for pregnancy diseases. Molecules of miRNAs are involved in several processes crucial for the development and functioning of the body. These processes include cell division and differentiation, programmed cell death, blood vessel formation or tumorigenesis, and the response to oxidative stress. MiRNAs affect the number of individual proteins in the body due to their ability to regulate gene expression at the post-transcriptional level, ensuring the normal course of many cellular processes. Based on the scientific facts available, this paper presents a compendium on the role of miRNA molecules in the miscarriage process. The expression of potential miRNA molecules as early minimally invasive diagnostic biomarkers may be evaluated as early as the first weeks of pregnancy, and may constitute a monitoring factor in the individual clinical care of women in early pregnancy, especially after the first miscarriage. To summarize, the described scientific data set a new direction of research in the development of preventive care and prognostic monitoring of the course of pregnancy.

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HMOX1 Participates in Pre-Eclampsia by Regulating the Proliferation, Apoptosis, and Angiogenesis Modulation Potential of Mesenchymal Stem Cells via VEGF

Shi,

2023

Biochem Genet

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Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia

Cited by 9 publications

References 370 publications

Truncated NLRC5 isoforms in human placenta: expression, regulation by miR-218-5p, and function in trophoblasts

Truncated NLRC5 isoforms in human placenta: expression, regulation by miR-218-5p, and function in trophoblasts

The role of miRNA molecules in the miscarriage process

HMOX1 Participates in Pre-Eclampsia by Regulating the Proliferation, Apoptosis, and Angiogenesis Modulation Potential of Mesenchymal Stem Cells via VEGF

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