The Role of Long Non-Coding RNAs in Trophoblast Regulation in Preeclampsia and Intrauterine Growth Restriction

Monteiro, Lara J.; Peñailillo, Reyna; Sánchez, Mario; Acuña-Gallardo, Stephanie; Monckeberg, Max; Ong, Ju Lynn; Choolani, Mahesh; Illanes, Sebastián E.; Nardocci, Gino

doi:10.3390/genes12070970

Cited by 18 publications

(10 citation statements)

References 157 publications

(178 reference statements)

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“…The same analysis uncovered that 40.6% (84/207) of ecDNAs overlapped with the coordinates of 1288 unique lncRNAs, 20.8% (43/207) of ecDNAs overlapped coordinates of 184 unique miRNAs, and 14.9% (31/207) of ecDNAs overlapped coordinates of 57 unique snoRNAs (Supplementary Data 11B). The results indicate that the function of these cyclic elements may be associated with lncRNA, tRNA, miRNA, snoRNA, etc., and some studies have demonstrated that under the conditions of stress, the expression of ncRNAs may change and participate in the progression of FGR (32,33).…”

Section: Biological Function Of Eccdnas/ecdnasmentioning

confidence: 99%

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Yang

Huang

et al. 2021

Front. Immunol.

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Many studies have confirmed that extrachromosomal circular DNAs (eccDNAs/ecDNAs) exist in tumor and normal cells independently of the chromosome and are essential for oncogene plasticity and drug resistance. Studies have confirmed that there are many eccDNAs/ecDNAs in maternal plasma derived from the fetus. Fetal growth restriction (FGR) is a pregnancy-related disease associated with high newborn morbidity and mortality. However, the characteristics and nature of eccDNAs/ecDNAs in FGR are poorly understood. This study aims to deconstruct the properties and potential functions of eccDNAs/ecDNAs in FGR. We performed circle-seq to identify the expression profile of eccDNAs/ecDNAs, analyzed by bioinformatics, and verified by real-time Polymerase Chain Reaction (PCR) combined with southern blot in FGR compared with the normal groups. A total of 45,131 eccDNAs/ecDNAs (including 2,118 unique ones) were identified, which had significantly higher abundance in FRG group than in normal group, and was bimodal in length, peaking at ~146bp and ~340bp, respectively. Gestational age may be one independent factor affecting the production of eccDNAs/ecDNAs, most of which come from genomic regions with high gene density, with a 4~12bp repeat around the junction, and their origin had a certain genetic preference. In addition, some of the host-genes overlapped with non-coding RNAs (ncRNAs) partially or even completely. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that host-genes on the differentially expressed eccDNAs/ecDNAs (DEEECs/DEECs) were mainly enriched in immune-related functions and pathways. The presence of some ecDNAs were verified, and whose variability were consistent with the circle-seq results. We identified and characterized eccDNAs/ecDNAs in placentas with FGR, and elucidated the formation mechanisms and the networks with ncRNAs, which provide a new vision for the screening of new biomarkers and therapeutic targets for FGR.

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Section: Biological Function Of Eccdnas/ecdnasmentioning

confidence: 99%

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Yang

Huang

et al. 2021

Front. Immunol.

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“…Several studies have investigated the role of lncRNAs in the pathogenesis of preeclampsia throughout their function in trophoblast migration, proliferation, and invasion [ 11 ]. The lncRNA UCA1 has been widely studied in cancer samples [ 30 , 31 ] and in trophoblast cells [ 32 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown the essential regulatory roles of lncRNA in preeclampsia [ 11 ]. Many differentially expressed lncRNAs in the placentas of preeclamptic patients have been reported, which suggests the potential role of lncRNAs in the pathogenesis of preeclampsia and their function in trophoblast cells [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of LOC101927355 as a Novel Biomarker for Preeclampsia

et al. 2022

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Preeclampsia, a disorder with a heterogeneous physiopathology, can be attributed to maternal, fetal, and/or placental factors. Long non-coding RNAs (lncRNAs) refer to a class of non-coding RNAs, the essential regulators of biological processes; their differential expression has been associated with the pathogenesis of multiple diseases. The study aimed to identify lncRNAs, expressed in the placentas and plasma of patients who presented with preeclampsia, as potential putative biomarkers of the disease. In silico analysis was performed to determine lncRNAs differentially expressed in the placentas of patients with preeclampsia, using a previously published RNA-Seq dataset. Seven placentas and maternal plasma samples collected at delivery from preterm preeclamptic patients (≤37 gestational weeks of gestation), and controls were used to validate the expression of lncRNAs by qRT-PCR. Six lncRNAs were validated and differentially expressed (p < 0.05) in the preeclampsia and control placentas: UCA1 and HCG4 were found upregulated, and LOC101927355, LINC00551, PART1, and NRAD1 downregulated. Two of these lncRNAs, HCG4 and LOC101927355, were also detected in maternal plasma, the latter showing a significant decrease (p = 0.03) in preeclamptic patients compared to the control group. In silico analyses showed the cytoplasmic location of LOC101927355, which suggests a role in post-transcriptional gene regulation. The detection of LOC101927355 in the placenta and plasma opens new possibilities for understanding the pathogenesis of preeclampsia and for its potential use as a biomarker.

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“…Long non-coding RNAs (lncRNAs) bear great responsibility for the occurrence and development of preeclampsia through modulation on the biological functions of trophoblasts, immune regulation, and epigenetic regulation [6–8]. Our bioinformatics analyses discovered TLR8-AS1 as a potential preeclampsia associated lncRNA.…”

Section: Introductionmentioning

confidence: 91%

Long non-coding RNA TLR8-AS1 induces preeclampsia through increasing TLR8/STAT1 axis

Peng¹,

Zhu

Guo

et al. 2023

Journal of Hypertension

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Objective: Our current study tried to assay the role of long noncoding RNAs (lncRNAs) TLR8-AS1 in regulating preeclampsia. Methods: TLR8-AS1 expression was examined in the clinical placental tissues of preeclampsia patients and the trophoblast cells induced by lipopolysaccharide (LPS). Then, different lentivirus was infected into trophoblast cells to study the role of TLR8-AS1 in cell functions. Furthermore, interactions among TLR8-AS1, signal transducer and activator of transcription 1 (STAT1) and toll-like receptor 8 (TLR8) were determined. A rat model of preeclampsia induced by N(omega)-nitro-L-arginine methyl ester was developed to validate the in-vitro findings. Results: High expression of TLR8-AS1 was detected in placental tissues of preeclampsia patients and LPS-induced trophoblast cells. In addition, overexpression of TLR8-AS1 arrested the proliferation, migration and invasion of trophoblast cells, which was related to the upregulation of TLR8 expression. Mechanistically, TLR8-AS1 recruited STAT1 to bind to the TLR8 promoter region, and thus promoted the transcription of TLR8. Meanwhile, overexpression of TLR8-AS1 was shown to aggravate preeclampsia by elevating TLR8 in vivo. Conclusion: Our study confirmed that TLR8-AS1 aggravated the progression of preeclampsia through increasing the expression of STAT1 and TLR8.

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The Role of Long Non-Coding RNAs in Trophoblast Regulation in Preeclampsia and Intrauterine Growth Restriction

Cited by 18 publications

References 157 publications

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Identification of LOC101927355 as a Novel Biomarker for Preeclampsia

Long non-coding RNA TLR8-AS1 induces preeclampsia through increasing TLR8/STAT1 axis

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