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      Long noncoding RNA SNHG12 promotes the proliferation, migration, and invasion of trophoblast cells by regulating the epithelial–mesenchymal transition and cell cycle

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          Abstract

          Objective

          The deficient placental blood perfusion caused by the attenuated infiltration of trophoblast cells is a key factor in the occurrence of preeclampsia (PE). Furthermore, the long noncoding (lnc)RNA SNHG12 (small nucleolar RNA host gene 12) can promote the proliferation and metastasis of multiple tumor cells. However, whether lncRNA SNHG12 affects proliferation and metastasis of trophoblast cells is unclear.

          Methods

          We examined the level of lncRNA SNHG12 in plasma and placenta of patients with PE and constructed trophoblast cells with overexpressed or knocked down SNHG12. CCK-8, wound healing, and Transwell assays were used to detect alterations in proliferation, migration, and invasion of trophoblast cells. Western blotting was used to detect proteins related to the epithelial–mesenchymal transition (EMT), and cell cycle assays clarified cell cycle distribution.

          Results

          LncRNA SNHG12 promoted the proliferation, migration, and invasion of trophoblast cells. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, β-catenin, and vimentin were positively correlated with SNHG12, and expression of E-cadherin was negatively correlated with SNHG12. SNHG12 also promoted the transition of trophoblast cells from G 0/G 1 to S phase.

          Conclusion

          Overall, lncRNA SNHG12 promoted the migration and invasion of trophoblast cells by inducing the progression of EMT.

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          Most cited references21

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          Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface.

          Trophoblasts, the specialized cells of the placenta, play a major role in implantation and formation of the maternal-fetal interface. Through an unusual differentiation process examined in this review, these fetal cells acquire properties of leukocytes and endothelial cells that enable many of their specialized functions. In recent years a great deal has been learned about the regulatory mechanisms, from transcriptional networks to oxygen tension, which control trophoblast differentiation. The challenge is to turn this information into clinically useful tests for monitoring placental function and, hence, pregnancy outcome.
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            Pathophysiology and Current Clinical Management of Preeclampsia.

            Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth weight babies. The early delivery of the baby, which becomes necessary for maintaining maternal well-being, makes preeclampsia the leading cause for preterm labor and infant mortality and morbidity. Currently, there is no cure for this pregnancy disorder. The current clinical management of PE is hydralazine with labetalol and magnesium sulfate to slow disease progression and prevent maternal seizure, and hopefully prolong the pregnancy. This review will highlight factors implicated in the pathophysiology of preeclampsia and current treatments for the management of this disease.
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              Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin.

              The objective of the present review is to synthesize the information on the cellular and molecular players responsible for maintaining a homeostatic balance between a naturally invasive human placenta and the maternal uterus in pregnancy; to review the roles of decorin (DCN) as a molecular player in this homeostasis; to list the common maladies associated with a break-down in this homeostasis, resulting from a hypo-invasive or hyper-invasive placenta, and their underlying mechanisms. We show that both the fetal components of the placenta, represented primarily by the extravillous trophoblast, and the maternal component represented primarily by the decidual tissue and the endometrial arterioles, participate actively in this balance. We discuss the process of uterine angiogenesis in the context of uterine arterial changes during normal pregnancy and preeclampsia. We compare and contrast trophoblast growth and invasion with the processes involved in tumorigenesis with special emphasis on the roles of DCN and raise important questions that remain to be addressed. Decorin (DCN) is a small leucine-rich proteoglycan produced by stromal cells, including dermal fibroblasts, chondrocytes, chorionic villus mesenchymal cells and decidual cells of the pregnant endometrium. It contains a 40 kDa protein core having 10 leucine-rich repeats covalently linked with a glycosaminoglycan chain. Biological functions of DCN include: collagen assembly, myogenesis, tissue repair and regulation of cell adhesion and migration by binding to ECM molecules or antagonising multiple tyrosine kinase receptors (TKR) including EGFR, IGF-IR, HGFR and VEGFR-2. DCN restrains angiogenesis by binding to thrombospondin-1, TGFβ, VEGFR-2 and possibly IGF-IR. DCN can halt tumor growth by antagonising oncogenic TKRs and restraining angiogenesis. DCN actions at the fetal-maternal interface include restraint of trophoblast migration, invasion and uterine angiogenesis. We demonstrate that DCN overexpression in the decidua is associated with preeclampsia (PE); this may have a causal role in PE by compromising endovascular differentiation of the trophoblast and uterine angiogenesis, resulting in poor arterial remodeling. Elevated DCN level in the maternal blood is suggested as a potential biomarker in PE.
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                Author and article information

                Journal
                J Int Med Res
                J. Int. Med. Res
                IMR
                spimr
                The Journal of International Medical Research
                SAGE Publications (Sage UK: London, England )
                0300-0605
                1473-2300
                12 June 2020
                June 2020
                : 48
                : 6
                : 0300060520922339
                Affiliations
                [1-0300060520922339]Department of Obstetrics, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu Province, China
                Author notes
                [*]Hairong Wang, Department of Obstetrics, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian No. 1 People’s Hospital, No. 6 Beijing West Road, Huaian City, Jiangsu Province, China, 223300. Email: hairongwang12@ 123456126.com
                Author information
                https://orcid.org/0000-0002-3947-0830
                Article
                10.1177_0300060520922339
                10.1177/0300060520922339
                7294383
                32529873
                cc1b7ae9-7991-4093-af32-354a3f5e21f6
                © The Author(s) 2020

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 14 November 2019
                : 3 April 2020
                Categories
                Validation Study
                Custom metadata
                corrected-proof
                ts2

                preeclampsia,trophoblast cells,lncrna snhg12,epithelial–mesenchymal transition (emt),cell cycle,long noncoding rna

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