The profile analysis of circular RNAs in human placenta of preeclampsia

Zhou, Wenbo; Wang, Huiyan; Wu, Xian; Long, Wei; Zheng, Fangxiu; Kong, Jing; Yu, Bin

doi:10.1177/1535370218813525

Cited by 38 publications

(33 citation statements)

References 40 publications

(49 reference statements)

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“…However, how these differentially expressed circRNAs affect the function of trophoblasts and thus participate in the development of PE, has not yet been reported. Previously, we identified differentially expressed circRNAs by RNA sequencing and verified their potential functions using qPCR and bioinformatics [12]. In particular, circRNA of pregnancy-associated plasma protein A (circ-PAPPA) (hsa circ 0088227), which originates from the pregnancy-associated plasma protein A (PAPPA) gene, attracted our attention.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…In another analysis, Zhou et al () found that 49 circRNAs differently expressed in placental tissues of women with pre‐eclampsia, compared to healthy pregnant women. Two of them were upregulated and others downregulated in pre‐eclampsic cases.…”

Section: Circrnas and Pre‐eclampsia: Latest Evidencementioning

confidence: 99%

“…One of the main functions of circRNAs is the activation of miRNA sponge which is involved in the pathogenesis of several diseases. On the other hand, some studies have suggested that circRNAs might play an important role in the pathogenesis of pre‐eclampsia through activating miRNA sponge method (Jiang et al, ; Qian et al, ; Zhou et al, ). Thus, we hypothesize that alterations in the levels of circRNAs may be involved in the pathogenesis of pre‐eclampsia and associated with its incidence.…”

Section: Circrnas and Pre‐eclampsia: Latest Evidencementioning

confidence: 99%

“…Two of them were upregulated and others downregulated in pre‐eclampsic cases. These three circRNAs, including circRNA_3286, circRNA_5593, and circRNA_3800, participated in several cellular functions in pre‐eclampsia through activating miRNA sponge (Zhou et al, ). In the latest related investigation, the expression of several mRNAs, ncRNAs, and circRNAs was profiled in women with pre‐eclampsia and healthy pregnant women to determine a potential prediction marker for pre‐eclampsia.…”

Section: Circrnas and Pre‐eclampsia: Latest Evidencementioning

confidence: 99%

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Could circRNA be a new biomarker for pre‐eclampsia?

Shafabakhsh

Mirhosseini

Chaichian

et al. 2019

Molecular Reproduction Devel

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Pre‐eclampsia is a devastating complication of pregnancy which is characterized by hypertension and proteinuria in pregnant women. Pre‐eclampsia is important as it is the leading cause of death. Moreover, untreated pre‐eclampsia might lead to other lethal complications, for both fetus and mother. Pre‐eclampsia can also affect the quality of life in affected women. Despite a large number of risk factors for pre‐eclampsia, these risk factors are able to detect just 30% of women who are susceptible to pre‐eclampsia. Heterogeneous manifestations of pre‐eclampsia necessitate the discovery of potential biomarkers required for its early detection. Circular RNAs (circRNAs) are a type of RNA which are more abundant, specific, and highly organized compared with other types of RNA. Accordingly, circRNAs have been suggested as one of the potential biomarkers for different diseases. Recently, researchers have shown interest in the effects of circRNAs in pre‐eclampsia, although the current evidence is limited. The majority of obstetricians are probably not aware of circRNAs as a useful biomarker. Here, we aimed to summarize recent supporting evidence and assess the mechanisms by which circRNAs are involved in pre‐eclampsia.

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“…long non-coding RNA, miRNA, circular RNA) in the placenta ( Cox et al , 2015 ). Differential placental expression of non-coding RNAs has been investigated in pre-eclampsia ( Gunel et al , 2017 ; Hu et al , 2018a ; Lykoudi et al , 2018 ; Zhou et al , 2018 ), GDM ( Li et al , 2015 ; Wang et al , 2019b ), IUGR or SGA pregnancies ( Wen et al , 2017 ; Ostling et al , 2019 ) and early pregnancy loss ( Hosseini et al , 2018 ). The use of RNA sequencing technologies to further characterize these non-coding RNAs provides a tantalizing approach to identify and develop new biomarkers and therapeutic targets for pregnancy complications.…”

Section: Knowledge Gaps and Future Directionsmentioning

confidence: 99%

Current approaches and developments in transcript profiling of the human placenta

Yong

Chan

2020

Human Reproduction Update

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BACKGROUND The placenta is the active interface between mother and foetus, bearing the molecular marks of rapid development and exposures in utero. The placenta is routinely discarded at delivery, providing a valuable resource to explore maternal-offspring health and disease in pregnancy. Genome-wide profiling of the human placental transcriptome provides an unbiased approach to study normal maternal–placental–foetal physiology and pathologies. OBJECTIVE AND RATIONALE To date, many studies have examined the human placental transcriptome, but often within a narrow focus. This review aims to provide a comprehensive overview of human placental transcriptome studies, encompassing those from the cellular to tissue levels and contextualize current findings from a broader perspective. We have consolidated studies into overarching themes, summarized key research findings and addressed important considerations in study design, as a means to promote wider data sharing and support larger meta-analysis of already available data and greater collaboration between researchers in order to fully capitalize on the potential of transcript profiling in future studies. SEARCH METHODS The PubMed database, National Center for Biotechnology Information and European Bioinformatics Institute dataset repositories were searched, to identify all relevant human studies using ‘placenta’, ‘decidua’, ‘trophoblast’, ‘transcriptome’, ‘microarray’ and ‘RNA sequencing’ as search terms until May 2019. Additional studies were found from bibliographies of identified studies. OUTCOMES The 179 identified studies were classifiable into four broad themes: healthy placental development, pregnancy complications, exposures during pregnancy and in vitro placental cultures. The median sample size was 13 (interquartile range 8–29). Transcriptome studies prior to 2015 were predominantly performed using microarrays, while RNA sequencing became the preferred choice in more recent studies. Development of fluidics technology, combined with RNA sequencing, has enabled transcript profiles to be generated of single cells throughout pregnancy, in contrast to previous studies relying on isolated cells. There are several key study aspects, such as sample selection criteria, sample processing and data analysis methods that may represent pitfalls and limitations, which need to be carefully considered as they influence interpretation of findings and conclusions. Furthermore, several areas of growing importance, such as maternal mental health and maternal obesity are understudied and the profiling of placentas from these conditions should be prioritized. WIDER IMPLICATIONS Integrative analysis of placental transcriptomics with other ‘omics’ (methylome, proteome and metabolome) and linkage with future outcomes from longitudinal studies is crucial in enhancing knowledge of healthy placental development and function, and in enabling the underlying causal mechanisms of pregnancy complications to be identified. Such understanding could help in predicting risk of future adversity and in designing interventions that can improve the health outcomes of both mothers and their offspring. Wider collaboration and sharing of placental transcriptome data, overcoming the challenges in obtaining sufficient numbers of quality samples with well-defined clinical characteristics, and dedication of resources to understudied areas of pregnancy will undoubtedly help drive the field forward.

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The profile analysis of circular RNAs in human placenta of preeclampsia

Cited by 38 publications

References 40 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

Could circRNA be a new biomarker for pre‐eclampsia?

Current approaches and developments in transcript profiling of the human placenta

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