Differentially expressed circular RNAs and the competing endogenous RNA network associated with preeclampsia.

Circular RNAs (circRNAs) are non-coding RNAs that are implicated in preeclampsia (PE) pathogenesis; however, their expression and functions in PE remain unclear. In this study, we aimed to investigate the expression of circRNAs in PE and construct a competing endogenous RNA (ceRNA) network, and analyze the associated pathways in PE pathogenesis. We performed circRNA sequencing to identify the differential expression profile of circRNAs in PE as compared to normal pregnancy. The circRNA candidates were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Subsequently, we used datasets from the GEO database to generate the interaction network between circRNAs, microRNAs (miRNAs), and mRNAs. GO and KEGG enrichment analyses were performed to understand the functional significance of the differentially expressed circRNAs in PE. We identified 361 differentially expressed circRNAs (252 upregulated and 109 downregulated) in preeclamptic placentas. Within the selected 31 circRNAs, 6 of them were verified by qRT-PCR. GO and KEGG analyses revealed the potential pathways affected by these circRNAs, e.g., T cell receptor signaling and MAP kinase pathways. A total of 134 miRNAs and 199 mRNAs were revealed to be differentially expressed in PE by analyzing datasets from the GEO database. The circRNA-miRNA-mRNA network comprised 206 circRNAs, 50 miRNAs, and 38 mRNAs. KEGG analysis of the 38 mRNAs included pathways involved in AMPK and PI3K-Akt signaling. Our results reported the differential expression profile of circRNAs and the circRNA-miRNA-mRNA network in PE, which provides potential therapeutic targets for this disease.

Ma B ，Zhao H ，Gong L ，Xiao X ，Zhou Q ，Lu H ，Cui Y ，Xu H ，Wu S ，Tang Y ，Ye Y ，Gu W ，Li X ... -  《-》

[Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta].

Liao LY ，Liu M ，Zhang YP ，Yin YX ，Wei XH ，Gao LB ，Zhou R ... -  《-》

Analysis of a circRNA-, miRNA-, and mRNA-associated ceRNA network reveals potential biomarkers in preeclampsia a ceRNA network in preeclampsia.

Xu X ，Lv S ，Xiao Z 《-》

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells.

Osteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human diseases. However, the potential role of circRNAs in postmenopausal osteoporosis (PMOP) remains largely unknown. The study aims to identify potential biomarkers and further understand the mechanism of PMOP by constructing a circRNA-associated ceRNA network. The PMOP-related datasets GSE161361, GSE64433, and GSE56116 were downloaded from the Gene Expression Omnibus (GEO) database and were used to obtain differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to determine possible relevant functions of differentially expressed messenger RNAs (mRNAs). The TRRUST database was used to predict differential transcription factor (TF)-mRNA regulatory pairs. Afterwards, combined CircBank and miRTarBase, circRNA-miRNA as well as miRNA-TF pairs were constructed. Then, a circRNA-miRNA-TF-mRNA network was established. Next, the correlation of mRNAs, TFs, and PMOP was verified by the Comparative Toxicogenomics Database. And expression levels of key genes, including circRNAs, miRNAs, TFs, and mRNAs in the ceRNA network were further validated by quantitative real-time PCR (qRT-PCR). Furthermore, to screen out signaling pathways related to key mRNAs of the ceRNA network, Gene Set Enrichment Analysis (GSEA) was performed. A total of 1201 DE mRNAs, 44 DE miRNAs, and 1613 DE circRNAs associated with PMOP were obtained. GO function annotation showed DE mRNAs were mainly related to inflammatory responses. KEGG analysis revealed DE mRNAs were mainly enriched in osteoclast differentiation, rheumatoid arthritis, hematopoietic cell lineage, and cytokine-cytokine receptor interaction pathways. We first identified 26 TFs and their target mRNAs. Combining DE miRNAs, miRNA-TF/mRNA pairs were obtained. Combining DE circRNAs, we constructed the ceRNA network contained 6 circRNAs, 4 miRNAs, 4 TFs, and 12 mRNAs. The expression levels of most genes detected by qRT-PCR were generally consistent with the microarray results. Combined with the qRT-PCR validation results, we eventually identified the ceRNA network that contained 4 circRNAs, 3 miRNAs, 3 TFs, and 9 mRNAs. The GSEA revealed that 9 mRNAs participate in many important signaling pathways, such as "olfactory transduction", "T cell receptor signaling pathway", and "neuroactive ligand-receptor interaction". These pathways have been reported to the occurrence and development of PMOP. To sum up, key mRNAs in the ceRNA network may participate in the development of osteoporosis by regulating related signal pathways. A circRNA-associated ceRNA network containing TFs was established for PMOP. The study may help further explore the molecular mechanisms and may serve as potential biomarkers or therapeutic targets for PMOP.

Dong Q ，Han Z ，Tian L 《Frontiers in Endocrinology》

Identification of LncRNA-miRNA-mRNA ceRNA network in hypoxia-induced HTR-8/SVneo cells for preeclampsia.

Preeclampsia (PE) is a common pregnancy complication, and placental hypoxia is one of its causes. We aimed to identify the transcriptional profile and construct a long non-coding RNAs (lncRNA)-centered competing endogenous RNAs (ceRNA) network in hypoxia-induced HTR8/SVneo cells. We used datasets from the GEO database to identify important pathways in PE. We performed microarray profiling and functional analysis to identify differentially expressed long non-coding RNAs (lncRNAs), differentially expressed profiles of microRNA (miRNAs), and differentially expressed profiles of messenger RNA (mRNAs) in hypoxia-induced HTR8/SVneo cells. The candidates were validated using quantitative reverse transcription polymerase chain reaction. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were performed to understand the functional significance of differentially expressed genes. Finally, we constructed an lncRNA-centered ceRNA network. Several hub genes were validated both in placentas from PE and normal pregnancy, and in hypoxia-induced HTR8/SVneo cells. The hypoxic response pathway was involved in the pathophysiology of PE. Subsequently, we identified 536 differentially expressed profiles of lncRNAs (183 upregulated and 353 downregulated), 46 differentially expressed profiles of miRNAs (35 upregulated and 11 downregulated), and 2782 differentially expressed profiles of mRNAs (DEmRNAs) (1031 upregulated and 1751 downregulated) in hypoxia-induced HTR8/SVneo cells. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed potential pathways affected by these genes, such as angiogenesis, the HIF-1 signaling pathway, and the PI3K-Akt signaling pathway. The ceRNA network comprised 35 lncRNAs, 11 miRNAs, 27 mRNAs, and 2 hub lncRNAs, which might play a vital role in placental functions and PE. Our results revealed the transcriptome profile and constructed an lncRNA-centered ceRNA network in hypoxia-induced HTR8/SVneo cells, thereby providing potential therapeutic targets for PE.

Liu Z ，Liu H ，Wang C ，Pei J ，Chu N ，Peng T ，Li X ，Gu W ，Tang Y ... -  《-》