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Revealing the action mechanisms of dexamethasone on the birth weight of infant using RNA-sequencing data of trophoblast cells

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      Dexamethasone (DEX) could induce low birth weight of infant, and low birth weight has close associations with glucocorticoid levels, insulin resistance, hypertension, and metabolic syndrome in adulthood. This study was designed to reveal the action mechanisms of DEX on the birth weight of infant.

      Using quantitative real-time polymerase chain reaction (qRT-PCR), trophoblast cells of human placenta were identified and the optimum treatment time of DEX were determined. Trophoblast cells were treated by DEX (DEX group) or ethanol (control group) (each group had 3 samples), and then were performed with RNA-sequencing. Afterward, the differentially expressed genes (DEGs) were identified by R package, and their potential functions were successively enriched using DAVID database and Enrichr method. Followed by protein–protein interaction (PPI) network was constructed using Cytoscape software. Using Enrichr method and TargetScan software, the transcription factors (TFs) and micorRNAs (miRNAs) targeted the DEGs separately were predicted. Based on MsigDB database, gene set enrichment analysis (GSEA) was performed.

      There were 391 DEGs screened from the DEX group. Upregulated SRR and potassium voltage-gated channel subfamily J member 4 ( KCNJ4) and downregulated GALNT1 separately were enriched in PDZ (an acronym of PSD-95, Dlg, and ZO-1) domain binding and Mucin type O-glycan biosynthesis. In the PPI network, CDK2 and CDK4 had higher degrees. TFs ATF2 and E2F4 and miRNA miR-16 were predicted for the DEGs. Moreover, qRT-PCR analysis confirmed that SRR and KCNJ4 were significantly upregulated.

      These genes might affect the roles of DEX in the birth weight of infant, and might be promising therapeutic targets for reducing the side effects of DEX.

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      Most cited references 48

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            Author and article information

            [a ]Department of Obstetrics and Gynecology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China
            [b ]Department of Obstetrics and Gynecology, Charite Medical University, Berlin, Germany.
            Author notes
            []Correspondence: Jinyi Tong, Department of Obstetrics and Gynecology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China (e-mail: JinyiTong45@ ).
            Medicine (Baltimore)
            Medicine (Baltimore)
            Wolters Kluwer Health
            January 2018
            26 January 2018
            : 97
            : 4
            29369181 5794365 MD-D-17-03006 10.1097/MD.0000000000009653 09653
            Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

            This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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