Hierarchical lncRNA regulatory network in early-onset severe preeclampsia

• Published in: BMC biology Vol. 22; no. 1; pp. 159 - 20
• Main Authors: Liu, Haihua, Wang, Zhijian, Li, Yanjun, Chen, Qian, Jiang, Sijia, Gao, Yue, Wang, Jing, Chi, Yali, Liu, Jie, Wu, Xiaoli, Chen, Qiong, Xiao, Chaoqun, Zhong, Mei, Chen, Chunlin, Yang, Xinping
• Format: Journal Article
• Language: English
• Published: London BioMed Central 29.07.2024; BioMed Central Ltd; BMC
• Subjects: Age; Biomedical and Life Sciences; Blood pressure; Cell cycle; Development and progression; Disease; Female; FLNB-AS1; Gene expression; Gene Regulatory Networks; Gene sequencing; Genes; Genetic aspects; Health aspects; Hierarchical regulatory network; HIF-1 signaling pathway; Humans; Hypotheses; JunB protein; Life Sciences; Long non-coding RNA; Non-coding RNA; Obstetrical research; Placenta; Placenta - metabolism; Pre-eclampsia; Pre-Eclampsia - genetics; Preeclampsia; Pregnancy; Proteins; Regulation of gene expression through RNA; Research Article; Risk factors; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal transduction; Transcription factors; Transcriptomes; China; Hierarchical regulatory network; HIF-1 signaling pathway; Preeclampsia; Long non-coding RNA; FLNB-AS1
• ISSN: 1741-7007; 1741-7007
• DOI: 10.1186/s12915-024-01959-1

Background Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. Results Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. Conclusions Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.