Bioinformatics-based identification of miRNA-, lncRNA-, and mRNA-associated ceRNA networks and potential biomarkers for preeclampsia

Yang

Computational and Mathematical Methods in Medicine

et al. 2022

Background. Preeclampsia (PE) is a multisystemic syndrome which has short- and long-term risk to mothers and children and has pluralistic etiology. Objective. This study is aimed at constructing a competitive endogenous RNA (ceRNA) network for pathways most related to PE using a data mining strategy based on weighted gene coexpression network analysis (WGCNA). Methods. We focused on pathways involving hypoxia, angiogenesis, and epithelial mesenchymal transition according to the gene set variation analysis (GSVA) scores. The gene sets of these three pathways were enriched by gene set enrichment analysis (GSEA). WGCNA was used to study the underlying molecular mechanisms of the three pathways in the pathogenesis of PE by analyzing the relationship among pathways and genes. The soft threshold power (β) and topological overlap matrix allowed us to obtain 15 modules, among which the red module was chosen for the downstream analysis. We chose 10 hub genes that satisfied ∣ log 2 Fold Change ∣ > 2 and had a higher degree of connectivity within the module. These candidate genes were subsequently confirmed to have higher gene significance and module membership in the red module. Coexpression networks were established for the hub genes to unfold the connection between the genes in the red module and PE. Finally, ceRNA networks were constructed to further clarify the underlying molecular mechanism involved in the occurrence of PE. 56 circRNAs, 17 lncRNAs, and 20 miRNAs participated in the regulation of the hub genes. Coagulation factor II thrombin receptor (F2R) and lumican (LUM) were considered the most relevant genes, and ceRNA networks of them were constructed. Conclusion. The microarray data mining process based on bioinformatics methods constructed lncRNA and miRNA networks for ten hub genes that were closely related to PE and focused on ceRNAs of F2R and LUM finally. The results of our study may provide insight into the mechanisms underlying PE occurrence.

Section: Introductionmentioning

confidence: 99%

ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis

Yang

Computational and Mathematical Methods in Medicine

et al. 2022

“…Indeed, reduced placental expression of LGALS13 (Galectin 13), a member of the glycan-binding proteins that regulate innate and adaptive immune responses, was found in women with preeclampsia ( Than et al, 2014 ). Similarly, the expression of SDC1, NPPB (natriuretic peptide B), GDF15 (growth differentiation factor 15), and ADAMTS6 (ADAM metallopeptidase with thrombospondin type 1 motif 6) all had a lower expression in our experimental exposures, and all are lower in preeclampsia ( Junus et al, 2014 ; Chen et al, 2016 ; Gandley et al, 2016 ; Jiang et al, 2020 ). In contrast, our data are inconsistent with respect to the expression of PAPPA2, a regulator of trophoblast invasion and migration, or MNDA (myeloid cell nuclear differentiation antigen), which exhibited a lower expression level in our paradigms but is elevated in placentas from women with preeclampsia ( Wagner et al, 2011 ; Kolialexi et al, 2017 ; Neuman et al, 2020 ).…”

Section: Discussionmentioning

confidence: 54%

RNA Network Interactions During Differentiation of Human Trophoblasts

Chu

Mouillet

Cao

et al. 2021

Front. Cell Dev. Biol.

In the human placenta, two trophoblast cell layers separate the maternal blood from the villous basement membrane and fetal capillary endothelial cells. The inner layer, which is complete early in pregnancy and later becomes discontinuous, comprises the proliferative mononuclear cytotrophoblasts, which fuse together and differentiate to form the outer layer of multinucleated syncytiotrophoblasts. Because the syncytiotrophoblasts are responsible for key maternal-fetal exchange functions, tight regulation of this differentiation process is critical for the proper development and the functional role of the placenta. The molecular mechanisms regulating the fusion and differentiation of trophoblasts during human pregnancy remain poorly understood. To decipher the interactions of non-coding RNAs (ncRNAs) in this process, we exposed cultured primary human trophoblasts to standard in vitro differentiation conditions or to conditions known to hinder this differentiation process, namely exposure to hypoxia (O2 < 1%) or to the addition of dimethyl sulfoxide (DMSO, 1.5%) to the culture medium. Using next generation sequencing technology, we analyzed the differential expression of trophoblastic lncRNAs, miRNAs, and mRNAs that are concordantly modulated by both hypoxia and DMSO. Additionally, we developed a model to construct a lncRNA-miRNA-mRNA co-expression network and inferred the functions of lncRNAs and miRNAs via indirect gene ontology analysis. This study improves our knowledge of the interactions between ncRNAs and mRNAs during trophoblast differentiation and identifies key biological processes that may be impaired in common gestational diseases, such as fetal growth restriction or preeclampsia.

“…A high level of maternal serum C3 in the first trimester is associated with an increased risk of preterm birth, which can be used for the early diagnosis and prognosis of preterm birth in pregnant women (49). C3 is implicated in the development of preeclampsia through bioinformatics-based identification (50). The serum concentration of C3 is elevated in women with preeclampsia compared with normal pregnant women (51).…”

Section: Discussionmentioning

confidence: 99%

Complement regulation in ovine lymph nodes during early pregnancy

et al. 2021

A fetus changes immune responses in the uterus and the maternal immune system, and lymph nodes are associated with regulating maternal adaptive immunity. Complement activation is associated with abnormal pregnancy in mice and humans. The aim of the present study was to explore the expression levels of complement components in maternal lymph nodes during early pregnancy in sheep. Maternal inguinal lymph nodes were sampled on day 16 of the estrous cycle, and days 13, 16 and 25 of gestation in ewes. Reverse transcription-quantitative PCR, western blotting and immunohistochemical analyses were used to detect the expression levels of complement components C1q, C1r, C1s, C2, C3, C4a, C5b and C9 in the lymph nodes. The results revealed that the protein and mRNA levels of C1q, C1s and C5b were enhanced during early pregnancy, and that C1r and C4a were upregulated at day 25 of pregnancy. The mRNA and protein levels of C2 and C9 peaked at day 16 of pregnancy, but C3 was decreased at day 25 of pregnancy. C3 protein was located in the subcapsular sinuses and lymph sinuses of the maternal lymph node. In summary, the present study detected changes in the expression levels of complement components in maternal lymph nodes, which may be associated with maternal immune regulation during early pregnancy in sheep.