Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines

Morales-Prieto, Diana M.; Barth, Emanuel; Murrieta-Coxca, José Martín; Favaro, Rodolfo R.; Gutiérrez-Samudio, Ruby N.; Chaiwangyen, Wittaya; Ospina‐Prieto, Stephanie; Gruhn, Bernd; Schleußner, E; Marz, Manja; Markert, Udo R.

doi:10.1016/j.placenta.2019.09.005

Cited by 7 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several miRNA species have been suggested to play a role in placental vascular formation by targeting VEGFA and other factors (reviewed in [51]). The miRNA profile in trophoblast cells changes with the gestational age and in presence of Leukemia Inhibitory Factor (LIF), a predominant cytokine present in the placenta during early pregnancy [19]. Here, we are reporting a general induction of miRNAs associated with angiogenesis or pregnancy pathologies in trophoblast cells upon IL-36 administration.…”

Section: Discussionmentioning

confidence: 94%

“…Previously, we have reported that cytokines present at the implantation site alter the expression of miRNAs in trophoblast cells by affecting pivotal intracellular pathways [19]. Thus, we explored the effect of exogenous IL-36 administration on miRNA expression in trophoblast cells.…”

Section: Microrna Expression Is Regulated By Il-36 Cytokines In Trophoblastic Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells

Murrieta-Coxca

Gutiérrez-Samudio

El-Shorafa

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

IL-36 cytokines (the agonists IL-36α, IL-36β, IL-36γ, and the antagonist IL-36Ra) are expressed in the mouse uterus and associated with maternal immune response during pregnancy. Here, we characterize the expression of IL-36 members in human primary trophoblast cells (PTC) and trophoblastic cell lines (HTR-8/SVneo and JEG-3) and upon treatment with bacterial and viral components. Effects of recombinant IL-36 on the migration capacity of trophoblastic cells, their ability to interact with endothelial cells and the induction of angiogenic factors and miRNAs (angiomiRNAs) were examined. Constitutive protein expression of IL-36 (α, β, and γ) and their receptor (IL-36R) was found in all cell types. In PTC, transcripts for all IL-36 subtypes were found, whereas in trophoblastic cell lines only for IL36G and IL36RN. A synthetic analog of double-stranded RNA (poly I:C) and lipopolysaccharide (LPS) induced the expression of IL-36 members in a cell-specific and time-dependent manner. In HTR-8/SVneo cells, IL-36 cytokines increased cell migration and their capacity to interact with endothelial cells. VEGFA and PGF mRNA and protein, as well as the angiomiRNAs miR-146a-3p and miR-141-5p were upregulated as IL-36 response in PTC and HTR-8/SVneo cells. In conclusion, IL-36 cytokines are modulated by microbial components and regulate trophoblast migration and interaction with endothelial cells. Therefore, a fundamental role of these cytokines in the placentation process and in response to infections may be expected.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Microrna Expression Is Regulated By Il-36 Cytokines In Trophoblastic Cellsmentioning

confidence: 99%

Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells

Murrieta-Coxca

Gutiérrez-Samudio

El-Shorafa

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…There have no reports about the relationship between miR-21 and CHD. While, some studied pointed out that the expression of miR-21 was signi cantly inhibited by the overexpression of STST3 [27,28]. Che X et al [29] pointed out FBN1 directly binds to FBXO2 can inactivating the cell cycle by polyubiquitination.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential miRNA-mRNA Regulatory Network in Tetralogy of Fallot: A Network Biology Approach

Wang

Lyu

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundTetralogy of Fallot (ToF) is one of the most prevalent and fatal birth defects. Its pathogenesis remains unknown and it’s not easily diagnosed at early stage. Therefore, it’s necessary to explore the critical regulators and molecular mechanism in ToF to find out novel molecular markers for early diagnosis.MethodsThree ToF datasets (GSE35490, GSE40128, GSE36761) were downloaded from the GEO database. The differentially expressed microRNAs (DEMs) and mRNAs (DEGs) were identified between ToF infants and normal infants after data preprocessing, followed by GO and KEGG analysis of DEGs. Then, PPI network and modular analysis were performed to identify the hub genes. Ultimately, potential miRNA-mRNA pathways in ToF were constructed based on the integrated data.Results22 overlapping DEMs were found in the GES35490 and GSE40128. Simultaneous, 181 intersected genes were found and identified as the significant DEGs including 84 down-regulated DEGs and 97 up-regulated DEGs. Further, 20 hub genes ranked by top 10% with high connectivity, including STAT3, FBN1, RUNX2, were found by PPT network and modular analysis. Furthermore, GO and KEGG analysis showed these DEGs were linked to cell cycle, apoptotic process, transcription activity and FOX signaling pathway. Additionally, we establish three potential miRNA-mRNA pathway, including miR-22-STAT3, miR-336/miR486-FBN1, miR-222-RUNX2, which can participate in the formation of ToF by cell cycle and transcription activity.ConclusionsThree miRNA-mRNA pathways were established and indicated cell cycle and transcription activity may be involved in the pathogenesis of ToF. Our study provided a novel bio-marker for early diagnosis of ToF.

show abstract

“…The similar response observed in proliferation and migration reported here in two trophoblast cell models demonstrates conserved functions of miR-519d-3p which may be relevant in vivo. Recently, we reported differences in the miRNA response of trophoblastic cell lines to leukemia inhibitory factor (LIF) [38]. Therefore, it may be expected that additional stimuli at the materno-fetal interface, such as growth factors or cytokines, may influence the function of miR-519d-3p.…”

Section: Discussionmentioning

confidence: 99%

MiR-519d-3p in Trophoblastic Cells: Effects, Targets and Transfer to Allogeneic Immune Cells via Extracellular Vesicles

Chaiwangyen

Murrieta-Coxca

Favaro

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Members of the placenta-specific miRNA cluster C19MC, including miR-519d, are secreted by fetal trophoblast cells within extracellular vesicles (EVs). Trophoblast-derived EVs can be internalized by the autologous trophoblast and surrounding maternal immune cells, resulting in coordination of cellular responses. The study of functions and targets of placental miRNAs in the donor and recipient cells may contribute to the understanding of the immune tolerance essential in pregnancy. Here, we report that miR-519d-3p levels correlate positively with cell proliferation and negatively with migration in trophoblastic cell lines. Inhibition of miR-519d-3p in JEG-3 cells increases caspase-3 activation and apoptosis. PDCD4 and PTEN are targeted by miR-519d-3p in a cell type-specific manner. Transfection of trophoblastic cell lines with miR-519d mimic results in secretion of EVs containing elevated levels of this miRNA (EVmiR-519d). Autologous cells enhance their proliferation and decrease their migration ability when treated with EVmiR-519d. NK92 cells incorporate EV-delivered miR-519d-3p at higher levels than Jurkat T cells. EVmiR-519d increases the proliferation of Jurkat T cells but decreases that of NK92 cells. Altogether, miR-519d-3p regulates pivotal trophoblast cell functions, can be transferred horizontally via EVs to maternal immune cells and exerts functions therein. Vesicular miRNA transfer from fetal trophoblasts to maternal immune cells may contribute to the immune tolerance in pregnancy.

show abstract

Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines

Cited by 7 publications

References 42 publications

Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells

Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells

Identification of Potential miRNA-mRNA Regulatory Network in Tetralogy of Fallot: A Network Biology Approach

MiR-519d-3p in Trophoblastic Cells: Effects, Targets and Transfer to Allogeneic Immune Cells via Extracellular Vesicles

Contact Info

Product

Resources

About