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miR-15b-AGO2 play a critical role in HTR8/SVneo invasion and in a model of angiogenesis defects related to inflammation.
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- Author(s): Yang, Ming; Chen, Yan; Chen, Liangju; Wang, Ke; Pan, Tianying; Liu, Xinghui; Xu, Wenming
- Source:
Placenta; May2016, Vol. 41, p62-73, 12p- Subject Terms:
RNA physiology; BLASTOCYST; BIOCHEMISTRY; CARRIER proteins; CELL lines; COMPARATIVE studies; EPITHELIAL cells; GENE expression; IN situ hybridization; INFLAMMATION; PHENOMENOLOGY; RESEARCH methodology; MEDICAL cooperation; NEOVASCULARIZATION; PLACENTA; PREECLAMPSIA; PREGNANCY; RESEARCH; RNA; EVALUATION research; LIPOPOLYSACCHARIDES; CHEMICAL inhibitors; PHYSIOLOGY; CELL physiology - Source:
- Additional Information
- Abstract:
Introduction: microRNAs (miRs) have been shown to play critical roles in the regulation of trophoblast and endothelial cell functions, and one significant finding concerning the miR-15/16 family is that most members of this family are highly expressed in endothelial cells and contribute to functions, such as tube formation. The interaction between trophoblast and endothelial cell play an important role in normal placentation process. Therefore, the aims of this study were to investigate the expression of miR-15b in human placenta and to uncover the potential role of miR-15b as well as its target functional loop in trophoblast and endothelial cells. Whether inflammation could modulate the expression of miR-15b and its down-stream target was further investigated. Additionally, the potential link between miR-15b deregulation and preeclampsia was also explored in the placenta of patients diagnosed with preeclampsia.Methods: The expression of miR-15b was studied in the placental tissue of a normal pregnancy using in situ hybridization, and the effects of miR-15b on proliferation, invasion, and angiogenesis were further explored in vitro using HTR-8/SVneo and HUVEC cell line models. A Lipopolysaccharides (LPS) treatment model in HTR-8/SVneo cell was utilized to explore the mechanism of how LPS treatment could lead to the activation of miR-15b expression. Western blot was used to detect the expression of proteins related to miR-15b mediated pathway in preeclamptic placentas.Results: miR-15b inhibits trophoblast cell invasion and endothelial cell tube formation by suppressing the expression of Argonaute 2 (AGO2), a major miRNA effecter protein. AGO2 is specifically localized to human placenta cytotrophoblast and endothelial cells, and it plays important roles in trophoblast cell invasion and endothelial cell tube formation. LPS treatment may lead to the overexpression of miR-15b and down-regulation of AGO2, which may be involved in shallow trophoblast cell invasion associated with the pathogenesis of preeclampsia. Chromatin immunoprecipitation assay indicates that increased occupancy of AGO2 to miR-15b promoter is responsible for the increased expression of miR-15b under the condition of LPS treatment. Furthermore, preeclamptic placentas have decreased expression of AGO2, but increased expression of miR-15b and TLR-4 compared to normal controls.Discussion: This is the first report about the function of AGO2 in human trophoblast and endothelial cells in the placenta. The data indicates that the aberrant expression of miR-15b contributes to abnormal placentation by targeting AGO2 mRNA. This study provides insight into the potential role of the miR-15b and AGO2 functional loop in the placentation process. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of Placenta is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
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