miR‐346 and miR‐582‐3p‐regulated EG‐VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9

Su, Mei Tsz; Tsai, Perng Jy; Tsai, Hui Ling; Chen, Yi Chi; Kuo, Pao Lin

doi:10.1002/biof.1325

Cited by 64 publications

(46 citation statements)

References 49 publications

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“…Furthermore, Su et al (30) reported that miR-346 regulated endocrine gland-vascular endothelial growth factor (EG-VEGF)-induced trophoblast invasion by inhibiting MMP-2 and MMP-9, although it had only a limited effect on TIMP-1 and TIMP-2. consistently in the present study, it was found that the effect of downregulated miR-346 on invasion-associated enzymes was similar to that of upregulated LRP6, which was found to promote the expression of MMP-2 and MMP-9 and to inhibit the expression of TIMP-1 and TIMP-2.…”

Section: Discussionmentioning

confidence: 99%

LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR‑346

Zhang

et al. 2020

Int J Mol Med

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Low-density lipoprotein receptor-related protein 6 (LRP6) promotes metastasis in numerous types of cancer; however, its role in trophoblast cells has been less frequently reported. In the present study, the effects of up-and downregulation of LRP6 on trophoblast cells were investigated accordingly. The study aimed to develop a therapeutic target for gestational choriocarcinoma. The expression levels of LRP6 in pre-eclampsia (PE) tissues, trophoblast cell lines and gestational choriocarcinoma cells were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPcR) assay. double-luciferase reporter analysis was conducted to detect the regulatory gene of LRP6. Furthermore, the proliferative, migratory and invasive abilities of trophoblasts and gestational choriocarcinoma cells were determined by ccK-8, wound healing, and Transwell assays, respectively. The expression levels of the genes and proteins of interest [matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2] associated with tumor cell invasion were measured by performing RT-qPcR and western blotting, respectively. The National center for Biotechnology Information database revealed that LRP6 was relatively highly expressed in placental tissues, but was poorly expressed in PE tissues and trophoblast cell lines. The upregulation of LRP6 not only increased the activity, migration and invasion of trophoblast cells, but it also promoted the expression of MMP-2 and MMP-9, whereas it inhibited the expression levels of TIMP-1 and TIMP-2. Such results followed the opposite trend to those of downregulation of LRP6 in gestational choriocarcinoma cells. Moreover, LRP6 was predicted to be the target gene for microRNA (miR)-346, which was highly expressed in PE tissues and trophoblast cell lines. The present study also revealed that LRP6 could reverse the effects of miR-346 on the proliferation, migration and invasion of trophoblast cells. Therefore, considered collectively, the results of the present study have demonstrated that LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR-346, and that LRP6 may serve as a potential target in cancer treatment.

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Section: Discussionmentioning

confidence: 99%

LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR‑346

Zhang

et al. 2020

Int J Mol Med

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“…Out of the 11 miRNAs downregulated in EVs from high oxygen tension on Day 3, miR-15a, miR-125a, miR-195, miR-125b, and miR-346 were previously investigated in embryonic or placental cells. The miRNA-346 has been described as a regulator of trophoblast invasion and migration in humans, while miR-195 is associated with an important paracrine effect on angiogenesis (Almeida et al, 2015;Su, Tsai, Tsai, Chen, & Kuo, 2016). The miR-125 family members, miR-125a and miR-125b play a role in cellular differentiation in mouse embryonic stem cells (K. Kim et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Oxygen tension modulates extracellular vesicles and its miRNA contents in bovine embryo culture medium

Andrade

Bomfim

Collado

et al. 2019

Molecular Reproduction Devel

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The biotechnology for in vitro embryo production is becoming increasingly popular, being applied to humans and domestic animals. Embryo development can be achieved with either 20% or 5% oxygen tension. The extracellular vesicles (EVs) are secreted by different cell types and carry bioactive materials. Our objective was to determine the secretion pattern and micro RNA (miRNA) contents of EVs released in the bovine embryo culture environment—embryo and cumulus cell monolayer—on Days 3 and 7 of in vitro culture under two different oxygen tensions: High (20%) and low (5%). The EVs were isolated from the medium and analyzed to determine size, concentration, and miRNA levels. EVs concentration in low oxygen tension increased on Day 3 and decreased on Day 7. Additionally, altered EV miRNAs derived from the embryo‐cumulus culture medium were predicted to regulate survival and proliferation‐related pathways on Days 3 and 7. Moreover, miR‐210 levels decreased in EVs isolated from the culture medium under high oxygen tension suggesting that this miRNA can be used as a marker for normoxia since it is associated with low oxygen tension. In summary, this study provides knowledge of the oxygen tension effects on EVs release and content, and potentially, on cell‐to‐cell communication during in vitro bovine embryo production.

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“…Using HTR8/SVneo, JEG-3 or BeWo trophoblast cell lines, several studies have suggested that miRNAs also regulate EVT motility by targeting other genes involved in regulating cell invasion. Both miR-346 and miR-582-3p targeted endocrine-gland-derived vascular endothelial growth factor (EG-VEGF) as well as matrix metalloproteinase 2 (MMP2) and MMP9, and strongly inhibited the migratory and invasive abilities of trophoblasts (Su et al 2017). Similarly, miR-93 (Pan et al 2017) and miR-204 (Yu et al 2015), which targeted MMP2 and MMP9, respectively, inhibit cell invasion.…”

Section: Mirnas In Trophoblast Differentiation Migration and Invasionmentioning

confidence: 99%

MicroRNAs: crucial regulators of placental development

Hayder¹,

O’Brien²,

Nadeem³

et al. 2018

Reproduction

119

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MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that are integral to a wide range of cellular processes mainly through the regulation of translation and mRNA stability of their target genes. The placenta is a transient organ that exists throughout gestation in mammals, facilitating nutrient and gas exchange and waste removal between the mother and the fetus. miRNAs are expressed in the placenta, and many studies have shown that miRNAs play an important role in regulating trophoblast differentiation, migration, invasion, proliferation, apoptosis, vasculogenesis/angiogenesis and cellular metabolism. In this review, we provide a brief overview of canonical and non-canonical pathways of miRNA biogenesis and mechanisms of miRNA actions. We highlight the current knowledge of the role of miRNAs in placental development. Finally, we point out several limitations of the current research and suggest future directions.

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miR‐346 and miR‐582‐3p‐regulated EG‐VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9

Cited by 64 publications

References 49 publications

LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR‑346

LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR‑346

Oxygen tension modulates extracellular vesicles and its miRNA contents in bovine embryo culture medium

MicroRNAs: crucial regulators of placental development

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