Up-regulation of miR-299 suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting HDAC2 in pre-eclampsia

Gao, Yu; She, Ruilian; Wang, Qian; Li, Yan; Zhang, Haiying

doi:10.1016/j.biopha.2017.11.053

Cited by 41 publications

(28 citation statements)

References 25 publications

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“…It has been confirmed that the invasiveness, differentiation and proliferation capabilities of trophoblasts are essential for implantation and placentation [28]. Importantly, growing evidences have demonstrated that miRNAs regulates the function of trophoblast cells [29][30][31]. In the current study, our findings firstly revealed that miR-338-5p overexpression blocked the growth of trophoblast cells.…”

Section: Discussionsupporting

confidence: 64%

miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction

Wen

Chen

et al. 2020

Reprod. Sci.

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Selective intrauterine growth restriction (sIUGR) is a disorder of monochorionic (MC) twin pregnancies. However, the underlying mechanism remains largely unknown. Trophoblast cells are the major component of the placenta. Dysfunction of trophoblast cells is associated with placental dysfunction. Our previous study identified miR-338-5p is downregulated in placenta tissues sharing larger twins of sIUGR. In the present study, we aimed to investigate the role of miR-338-5p in trophoblast cells and explored its target. Our results further indicated that miR-338-5p was downregulated in placental tissues supporting larger twins of sIUGR, whereas epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was upregulated. Moreover, miR-338-5p overexpression suppressed the growth and invasion of trophoblast cells. Importantly, results from luciferase reporter assay demonstrated that miR-338-5p bound on the 3′-UTR of EFEMP1. miR-338-5p suppressed the growth and invasion of trophoblast cells via targeting EFEMP1. Further, miR-338-5p/EFEMP1 might disrupt the function of trophoblast cells via inhibiting the phosphorylation of AKT.

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Section: Discussionsupporting

confidence: 64%

miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction

Wen

Chen

et al. 2020

Reprod. Sci.

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“…Given our prediction that HEa miRNAs interfere with signaling pathways governing fetal and placental development (8), we conducted a literature review of reports on HEa miRNA levels in gestational pathologies caused by poor placentation (26, 27, 28). Surprisingly, placental and plasma levels of 8 of 11 HEa miRNAs were significantly dysregulated in one or more of these gestational pathologies with expression of the majority of these eight miRNAs altered in both fetal growth restriction and preeclampsia (Fig 1A) (29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49), both of which are characterized by poor placental invasion (50, 51, 52, 53, 54, 55, 56).…”

Section: Resultsmentioning

confidence: 99%

Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation

et al. 2019

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Prenatal alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, although the linking causal mechanisms are unclear. We previously identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following PAE. Here, we investigated whether these HEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial–mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and that HEamiRNAs collectively, but not individually, mediate placental EMT inhibition. HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intravascular administration of the pooled murine-expressed HEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited the expression of pro-EMT transcripts in the placenta. Our data suggest that HEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.

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“…Previous studies have reported that miRNAs are aberrantly expressed in PE placenta tissues and are involved in several pathophysiological processes, including the invasion and migration of trophoblast cells (8,(23)(24)(25)(26)(27). For example, miR-136 was shown to be increased in PE placenta tissue, where it inhibited the invasion of trophoblast cells (28); Xue et al (29) found that miR-34a-5p expression levels were increased in patients with PE, and these upregulated levels suppressed the invasion and migration of trophoblast cells through directly targeting SMAD4; Guo et al (30) revealed that miR-423-5p expression levels were increased in the blood plasma of pregnant women with PE, which effectively inhibited migration and invasion through targeting IGF2BP1 in HTR-8/SVneo cells; and Gao et al (31) found that increased expression levels of miR-299 suppressed the invasion and migration of HTR-8/SVneo trophoblast cells through targeting HDAC2 in PE. These previous findings suggested that miRNAs may be an attractive therapeutic target against PE.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑491‑5p inhibits trophoblast cell migration and invasion through targeting matrix metalloproteinase‑9 in preeclampsia

Liu

Zhou

et al. 2020

Mol Med Rep

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Insufficient invasion of trophoblasts is correlated with the development of preeclampsia (PE). MicroRNA (miR)-491-5p has been reported to be implicated in human cancer cell invasion; however, whether miR-491-5p is involved in the development of PE remains largely unclear. The aim of the present study was to investigate the role of miR-491-5p in trophoblastic invasion in vitro and to determine its underlying mechanism of action. The expression levels of miR-491-5p were validated using reverse transcription-quantitative PCR. The effects of miR-491-5p on trophoblast cell invasion were evaluated in vitro. Then, the association between miR-491-5p and its downstream target was investigated in both cell lines and clinical specimens. miR-491-5p expression levels were observed to be significantly increased in the placental tissues from patients with PE. The invasive capacity of HTR-8/SVneo trophoblast cells was suppressed following the upregulation of miR-491-5p and increased following the inhibition of miR-491-5p. Matrix metalloproteinase-9 (MMP-9), a well-known regulator of trophoblast cell invasion, was discovered to be a direct target of miR-491-5p in HTR-8/SVneo trophoblast cells. Moreover, miR-491-5p expression levels were found to be inversely correlated with MMP-9 expression levels in placental tissues from patients with PE. The overexpression of MMP-9 partly attenuated the inhibitory effects of miR-491-5p on HTR-8/SVneo trophoblast cells invasion. Collectively, these findings suggested that the aberrant expression of miR-491-5p may contribute to PE through suppressing trophoblast invasion, thus highlighting the novel roles of miR-491-5p in the molecular pathogenesis of PE. The present study also showed that the miR-491-5p/MMP-9 axis may be an effective biomarker or a viable drug target for therapeutic intervention in PE.

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Up-regulation of miR-299 suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting HDAC2 in pre-eclampsia

Cited by 41 publications

References 25 publications

miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction

miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction

Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation

MicroRNA‑491‑5p inhibits trophoblast cell migration and invasion through targeting matrix metalloproteinase‑9 in preeclampsia

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