Competing endogenous RNA expression profiling in pre-eclampsia identifies hsa_circ_0036877 as a potential novel blood biomarker for early pre-eclampsia

Hu, Xiaopeng; Ao, Junping; Li, Xinyue; Zhang, Huijuan; Wu, Ji; Cheng, Weiwei

doi:10.1186/s13148-018-0482-3

Cited by 87 publications

(64 citation statements)

References 45 publications

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“…Studies on PE and circRNAs are still in the preliminary stages, but in a recent report, differential circRNA expression profiles were observed in blood and placenta tissues of PE patients [11,25]. Using clinical correlation studies, some differentially expressed circRNAs, such as hsa circ 0036877, circRNA-0004904, and circRNA-0001855, might function as competing endogenous RNAs and serve as novel blood biomarkers for the early prediction of PE [26,27]. In the present study, we evaluated the possible functions of a circRNA, circPAPPA, which we previously characterized.…”

Section: Discussionmentioning

confidence: 99%

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

et al. 2019

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Preeclampsia (PE) is the main cause of maternal death in primipara, and commonly results in severe maternal and neonatal complications such as multiple organ dysfunction syndrome. However, the exact pathogenesis of this disease remains unclear. Circular RNAs (circRNAs) are noncoding RNAs that have been shown to be extensively involved in numerous physiological processes, but there is limited knowledge of their functions and mechanisms in PE. In the present study, we found the expression of a circRNA, hsa_circ_0088227 (circRNA of pregnancy-associated plasma protein A, circPAPPA), was down-regulated in both placenta and plasma samples from subjects with PE. Knockdown of circPAPPA led to decreased proliferation and invasion in HTR8-S/Vneo trophoblast cells. miR-384 was identified as a direct target of circPAPPA, and the gene encoding signal transducer and activator of transcription 3 (STAT3) was targeted by miR-384. We found that miR-384 was unregulated in PE, and overexpression of miR-384 could inhibit cell proliferation and invasion. In addition, we showed that the expression of STAT3 was decreased with knockdown of circPAPPA or the overexpression of miR-384 in trophoblast cells, but this decrease was partially reversed when co-transfection was performed with mimics of miR-384 inhibitor and si-circPAPPA. Together, these results suggest that down-regulation of circPAPPA facilitates the onset and development of PE by suppressing trophoblast cells, with involvement of the miR-384/STAT3 signaling pathway. Our study significantly increases the understanding of the occurrence and development of PE, and also provides a molecular target for the treatment of this disorder.

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Section: Discussionmentioning

confidence: 99%

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

et al. 2019

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“…They have been found implicated with various cancers, including colorectal, lung, and cervical cancer . Hitherto noticed features of circRNA are mainly based on evidence gathered from human, and studies on other species are insufficient …”

Section: Introductionmentioning

confidence: 99%

“…[18][19][20] Hitherto noticed features of circRNA are mainly based on evidence gathered from human, and studies on other species are insufficient. [21][22][23][24] This study aims to explore the multiple factors that potentially lead to high abortion frequency exist in SCNT fetus generation during late gestation. To this end, we collected two aberrant pregnant placenta (abnormal group, AG) and three normal pregnant placenta (normal group, NG) at late gestation (180-210 days) of bovine SCNT fetus.…”

Section: Introductionmentioning

confidence: 99%

CircRNA expression profile of bovine placentas in late gestation with aberrant SCNT fetus

Gao

Wang

et al. 2019

Clinical Laboratory Analysis

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BackgroundsOne of the limitations of somatic cell nuclear transfer (SCNT) strategy to generate genetically modified offspring is the low birth rate. Placental dysfunction is one of the causes of abortion. Circular RNA (circRNA) is noncoding RNA which functions as microRNA (miRNA) sponges in biological processes.MethodsTwo aberrant pregnant placenta (aberrant group, AG) and three normal pregnant placenta (normal group, NG) during late gestation (180‐210 days) with bovine SCNT fetus were collected for high‐throughput sequencing and analyzed. The host genes of differentially expressed (DE) circRNAs were predicted. And the microRNAs (miRNAs) which could interact with DE circRNAs were analyzed. Then, the expressional level of partial DE circRNAs and corresponding host genes was verified through qRT‐PCR. At last, the function of host genes was analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).ResultsAltogether 123 differentially expressed circRNAs between two groups were identified, which were found related to 60 host genes and 32 miRNAs. The top 10 upregulated circRNAs were bta_circ_0012985, bta_circ_0013071, bta_circ_0013074, bta_circ_0016024, bta_circ_0013068, bta_circ_0008816, bta_circ_0012982, bta_circ_0013072, bta_circ_0019285, and bta_circ_0013067. The top 10 downregulated circRNAs were bta_circ_0024234, bta_circ_0017528, bta_circ_0008077, bta_circ_0003222, bta_circ_0007500, bta_circ_0020328, bta_circ_0011001, bta_circ_0016364, bta_circ_0008839, and bta_circ_0016049. The qRT‐PCR results showed consistent trend with sequencing analysis result, while host genes had no statistic difference. The GO and KEGG analyses of the host genes suggested that abnormal circRNA expression may play multiple roles in placental structure and dysfunction.ConclusionThe abnormal circRNA expression may be one of reasons of placental dysfunction, leads to abortion of bovine SCNT fetus.

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“…8 In addition, circRNAs possess a great potential as disease biomarkers for diagnosis, prognosis and targeted therapy, especially in tumor 9,10 and neurodegeneration. 14,15 Yet, whether specific circRNAs could be biomarkers of fetal growth restriction (FGR) is unknown and requires further analysis and investigation, especially in clinical research. 14,15 Yet, whether specific circRNAs could be biomarkers of fetal growth restriction (FGR) is unknown and requires further analysis and investigation, especially in clinical research.…”

mentioning

confidence: 99%

“…[11][12][13] In obstetrics and gynecology, the relationship between circRNAs and pre-eclampsia (PE) has been explored in several studies. 14,15 Yet, whether specific circRNAs could be biomarkers of fetal growth restriction (FGR) is unknown and requires further analysis and investigation, especially in clinical research.…”

mentioning

confidence: 99%

Differentially expressed circular RNAs in maternal and neonatal umbilical cord plasma from SGA compared with AGA

Wang

Dang

et al. 2019

J of Cellular Biochemistry

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Small for gestational age (SGA) has a high risk of mortality and morbidity and is common in obstetrics. To date, no effective prediction and treatment tools are available. Acting as microRNA (miRNA) sponges and disease biomarkers are clear functions of circular RNAs (circRNAs). However, it is still unknown what role circRNAs act in SGA. To explore the role of circRNAs in SGA, circRNA expression patterns of the umbilical cord and maternal plasma in SGA was assessed. We first evaluated circRNAs in umbilical cord blood of the SGA and appropriate for gestational age (AGA) groups by microarray sequencing. In total, 170 340 circRNAs were sequenced, and 144 circRNAs were significantly upregulated while 977 were markedly downregulated. Has_circRNA15994‐13, has_circ_0001359, and has_circ_0001360 were abundant and differentially expressed between the SGA and AGA groups, and confirmed in the umbilical cord and maternal blood specimens by reverse transcription polymerase chain reaction. By combining miRNA microarray data of the SGA placenta tissue in NCBI, it was found that two miRNAs were both hsa_circRNA15994‐13 targets and differentially expressed, including hsa‐miR‐3619‐5p and hsa‐miR‐4741. Further KEEG analysis revealed that the most significant pathway enriched by hsa‐miR‐3619‐5p was Wnt signaling that is closely related to SGA; meanwhile, previous reports demonstrated that hsa‐miR‐3619‐5p directly binds to β‐catenin to accommodate the Wnt/β‐catenin pathway, whereby the suggestive hsa_circRNA15994‐13 → hsa‐miR‐3619‐5p → β‐catenin signaling pathway may play an important part in SGA.

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Competing endogenous RNA expression profiling in pre-eclampsia identifies hsa_circ_0036877 as a potential novel blood biomarker for early pre-eclampsia

Cited by 87 publications

References 45 publications

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

CircRNA expression profile of bovine placentas in late gestation with aberrant SCNT fetus

Differentially expressed circular RNAs in maternal and neonatal umbilical cord plasma from SGA compared with AGA

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