Mechanistic Insight into Long Noncoding RNAs and the Placenta

McAninch, Dale; Roberts, Claire T.; Bianco‐Miotto, Tina

doi:10.3390/ijms18071371

Cited by 61 publications

(48 citation statements)

References 118 publications

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“…An equal amount of protein (30 µg) was loaded in each sample well. The protein samples were separated using SDS-PAGE and transferred to PVDF membranes (Millipore) as described previously (Maryam et al, 2017). The membranes were incubated with diluted primary antibodies (mouse antihuman monoclonal antibody) AKT1 (1:300, ab124341, Abcam, Inc., Cambridge, MA, United States), PI3K (1:100, ab28356, Abcam), PTEN [1:200, #9188, Cell Signaling Technology (CST), Inc., Beverly, MA, United States] MMP9 (1:100, #13667S, CST), TP53 (1:100, #2527, CST), GADPH (1:2000, sc-32233, Santa Cruz, CA, United States) at 4 • C overnight.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Zheng

Hou

et al. 2020

Front. Genet.

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Preeclampsia is a lethal pregnancy specific hypertensive disorder involving multisystem. Despite extensive studies to investigate the causes of preeclampsia, the pathogenesis still remains largely unknown. Long non-coding RNAs (lncRNAs) are a diverse class of non-translated RNAs which play a crucial part in various biological phenomena. Although lncRNA Growth Arrest-Specific 5 (GAS5) aberrantly expressed in multiple cancer tissues and is implicated in multiple biological processes of tumor cells, little is known about its role in preeclampsia. In this study, 40 patients with preeclampsia and 32 gestational age matched normotension pregnant women were recruited. Using quantitative real-time polymerase chain reaction (qRT-PCR), we found higher expression of GAS5 in placenta of preclamsia affected women. The level of GAS5 existed strongly in correlation with Thrombin Time indicating coagulation function and other clinical parameters by Pearson correlation analysis. Then we constructed the GAS5 lentivirus expression vectors and transfected into human trophoblast cell lines HTR-8/SVneo and JEG-3. Using in vitro cell culture studies, we found an inhibited effect of GAS5 on proliferative ability, migratory ability and invasive ability however; no effect on apoptosis was detected. Further mechanistic analysis found that GAS5 modulated microRNA-21 (miR-21) in an opposite variation tendency by qRT-PCR and rescue experiment. In addition, inhibition of GAS5 promoted the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53 as evident from our qRT-PCR and western blot analyses. Thus, we suggested that GAS5 might involve in pregnancy with preeclampsia by influencing the biological functions of trophoblast cells through the regulation of miR-21 and activation of PI3K/AKT signaling pathway and its downstream targets, which may contribute to reveal the nature of preeclampsia.

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Section: Western Blot Analysismentioning

confidence: 99%

“…Although the number of lncRNAs identified increases continuously, the biological significances and functions of the majorities remain unknown. They promisingly and strongly influence the development and health, associated with a variety of human complicated diseases (McAninch et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Zheng

Hou

et al. 2020

Front. Genet.

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“…It is considered that these lncRNAs are regulated through effects such as miRNA sponging, chromatin remodelling and epigenetic modification . It is interesting to note that recently, an increasing number of studies have validated the fact that lncRNAs might be associated with diverse human pregnancy‐related disorders, especially PE …”

Section: Introductionmentioning

confidence: 99%

Down‐regulated lncRNA AGAP2‐AS1 contributes to pre‐eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype

Xia

Jiang

et al. 2020

J Cellular Molecular Medi

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Recently, growing evidence has shown that aberrant long non-coding RNA (lncRNA) expression in conjunction with an impaired trophoblastic phenotype could implicate the pathological process of pre-eclampsia (PE). However, only a small portion of lncR-NAs has been characterized with regard to the function and molecular mechanisms involved in PE. There are still gaps in the available knowledge; as a result, there are currently only a few applicable treatments for PE in the context of lncRNA. Here, we found that lncRNA AGAP2-AS1 is abnormally down-regulated in severe PE placenta tissues. Using human trophoblasts, we established that AGAP2-AS1 knockdown could inhibit trophoblasts proliferation and invasion and promote cell apoptosis.Further, we showed that overexpression of AGAP2-AS1 substantially stimulated the development of the trophoblastic phenotype. Through high-throughput sequencing analysis, we demonstrated that silencing of AGAP2-AS1 favourably regulated various genes which are relevant to trophoblastic growth and invasion. Mechanistically, AGAP2-AS1 promoted the suppressor protein, Jun dimerization protein 2 (JDP2), by sponging miR-574-5p. Resultantly, further impairment of the trophoblastic phenotype was achieved by way of inhibiting cell growth, apoptosis and invasion. We also determined that the expression of AGAP2-AS1 could be mediated by FOXP1. Our results showed that the down-regulated expression of lncRNA AGAP2-AS1 might serve as a key suppressor in PE via inhibition of JDP2 at the post-transcriptional level by competing for miR-574; thus, this presents a novel therapeutic strategy for PE. K E Y W O R D SAGAP2-AS1, FOXP1, JDP2, pre-eclampsia, trophoblastic phenotype

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“…Excessive apoptosis of trophoblast cells, poor invasion of the uterine wall by trophoblasts, and impaired remodeling of spiral arteries at the maternal‐fetal interface are major abnormal placentation events that are closely related to PE . According to the literature, noncoding RNAs play a major role in the regulation of embryonal growth; as a result, they present new areas of investigation on placental differentiation and function …”

Section: Introductionmentioning

confidence: 99%

“…11 According to the literature, noncoding RNAs play a major role in the regulation of embryonal growth; as a result, they present new areas of investigation on placental differentiation and function. 12 The long noncoding RNAs (lncRNAs) are transcribed RNA molecules with a length more than 200 nucleotides. They lack open reading frames which have key regulatory effects in both transcription and post-transcription.…”

mentioning

confidence: 99%

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

et al. 2019

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The effect of DNA methylation on gene expression triggered it as a susceptibility factor in various diseases including preeclampsia (PE). The pathogenesis of PE is closely associated with the methylation status and genetic variants of relevant genes. Therefore, the aim of the study was to investigate the possible impacts of the placental DNA methylation and rs3741219, rs217727, and rs2107425 polymorphisms of the H19 gene on the PE susceptibility as well as the its mRNA expression. Moreover, eight haplotypes of three loci in the H19 gene were analyzed. In this case‐control study, the placentas of 107 preeclamptic and 113 non‐preeclamptic women were collected after delivery. The methylation status was assessed by methylation‐specific polymerase chain reaction (PCR). The H19 polymorphisms were genotyped using polymerase chain reaction‐restriction fragment length polymorphism or amplification refractory mutation system‐polymerase chain reaction methods. The quantitative real time PCR was used for mRNA expression assay. The placental H19 rs3741219 and rs2107425 polymorphisms were not associated with PE. However, H19 rs217727CT and TT genotypes might be associated with a 9.2‐ and 17.7‐fold increased risk of PE, respectively. The Trs3741219 Crs217727 Crs2107425 and Trs3741219 Crs217727 Trs2107425 haplotypes were significantly lower, whereas the Trs3741219 Trs217727 Crs2107425 and Crs3741219 Trs217727 Crs2107425 haplotypes were significantly higher in PE women. Promoter but not upstream region hypermethylation of H19 gene could be led to decreased risk of PE (MM vs. UM + UU). No significant difference was observed in the placental mRNA expression between two groups. The H19 expression was significantly higher in women with unmethylated (UU), compared to methylated promoter (MM). The H19 expression was 17‐ and 15‐fold higher in H19‐rs2107425 CC and CT genotypes in PE women. In conclusion, the H19 rs2107425 polymorphism was associated with a higher risk of PE and increased H19 mRNA expression. The promoter hypermethylation of H19 gene was associated with a lower risk of PE and decreased H19 mRNA expression.

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Mechanistic Insight into Long Noncoding RNAs and the Placenta

Cited by 61 publications

References 118 publications

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Down‐regulated lncRNA AGAP2‐AS1 contributes to pre‐eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

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