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miR-542-3p 的缺失可增强人子宫内膜基质细胞的 IGFBP-1 表达。

Loss of miR-542-3p enhances IGFBP-1 expression in decidualizing human endometrial stromal cells.

机构信息

Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, Japan.

Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka city, Saitama, Japan.

出版信息

Sci Rep. 2017 Jan 4;7:40001. doi: 10.1038/srep40001.

Abstract

Endometrial decidualization represents an essential step for the successful implantation of the embryo; however, the molecular mechanism behind this differentiation process remains unclear. This study aimed to identify novel microRNAs (miRNAs) involved in the regulation of decidual gene expression in human endometrial stromal cells (HESCs). An in vitro analysis of primary undifferentiated and decidualizing HESCs was conducted. HESCs were isolated from hysterectomy specimens from normally cycling premenopausal women with uterine fibroids, who were not on hormonal treatment at the time of surgery. Primary HESCs were expanded in culture and decidualized with 8-bromo-cyclic adenosine monophosphate and medroxyprogesterone acetate. Microarray analysis identified six miRNAs differentially expressed in response to decidualization of HESCs. All but one miRNA were downregulated upon decidualization, including miR-542-3p. We demonstrated that miR-542-3p overexpression inhibits the induction of major decidual marker genes, including IGFBP1, WNT4 and PRL. In addition, miR-542-3p overexpression inhibited the morphological transformation of HESCs in response to deciduogenic cues. A luciferase reporter assay confirmed that the 3'-untranslated region of IGFBP1 mRNA is targeted by miR-542-3p. The results suggest that miR-542-3p plays an important role in endometrial decidualization by regulating the expression of major decidual marker genes.

摘要

子宫内膜蜕膜化是胚胎成功着床的关键步骤;然而,这一分化过程的分子机制尚不清楚。本研究旨在鉴定参与人子宫内膜基质细胞(HESC)蜕膜基因表达调控的新型 microRNA(miRNA)。对未分化和诱导分化的原代 HESC 进行体外分析。HESC 从患有子宫肌瘤的正常月经周期绝经前妇女的子宫切除术标本中分离出来,这些妇女在手术时未接受激素治疗。原代 HESC 在培养基中扩增,并通过 8-溴环磷酸腺苷和甲羟孕酮诱导其蜕膜化。微阵列分析鉴定出 6 种在 HESC 蜕膜化过程中差异表达的 miRNA。除了 miR-542-3p 外,所有 miRNA 的表达在蜕膜化后均下调。我们证明 miR-542-3p 的过表达抑制主要蜕膜标记基因 IGFBP1、WNT4 和 PRL 的诱导。此外,miR-542-3p 的过表达抑制了 HESC 对蜕膜诱导信号的形态转化。荧光素酶报告基因检测证实 IGFBP1 mRNA 的 3'非翻译区是 miR-542-3p 的靶标。结果表明,miR-542-3p 通过调节主要蜕膜标记基因的表达在子宫内膜蜕膜化中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/5209665/471f786e1a36/srep40001-f1.jpg

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