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miRNA-34a-5p 在子宫内膜干细胞中对 VEGFA 的下调导致子宫内膜异位症的发病机制。

miRNA‑34a‑5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis.

机构信息

Department of Gynaecology and Obstetrics, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.

出版信息

Mol Med Rep. 2017 Dec;16(6):8259-8264. doi: 10.3892/mmr.2017.7677. Epub 2017 Sep 29.

Abstract

Endometrial-derived stem cells (EnSCs) serve an important role in the development of endometriosis via retrograde menstruation. Abnormal expression of miRNAs in EnSCs is involved in the etiology of endometriosis, however, the mechanisms remain unclear. The aim of the present study was to investigate the expression of miR‑34a‑5p and VEGFA in endometrial samples from patients with or without endometriosis, and then examine the underlying mechanism of microRNA‑34a‑5p regulation of VEGFA in EnSCs. Endometrial samples from patients with or without endometriosis were collected, and miR‑34a‑5p expression in the two groups was measured using RT‑PCR. Human endometrial‑derived stem cells (hEnSCs) were isolated from these endometrial samples, and hEnSCs were transfected with the miR‑34a‑5p mimics or control miRNAs. qPCR and western blotting were performed to assess the effects of miR‑34a‑5p on the expression of VEGFA in hEnSCs, and cell growth was assessed by an MTT assay. miR‑34a‑5p was significantly downregulated in patients with endometriosis when compared with that of those without endometriosis. VEGFA expression levels in hEnSCs with an overexpression of miR‑34a‑5p were significantly reduced when compared with those in the negative control (P<0.01). In addition, the upregulation of miR‑34a‑5p suppressed EnSCs proliferation by targeting the 3' untranslated region of VEGFA. miR‑34a‑5p provides a novel avenue for the understanding of the development of endometriosis, and may facilitate the development of potential therapeutics against endometriosis.

摘要

子宫内膜来源的干细胞(EnSCs)在逆行月经中通过逆行月经在子宫内膜异位症的发展中起重要作用。EnSCs 中 miRNAs 的异常表达参与了子宫内膜异位症的病因,但机制尚不清楚。本研究旨在探讨子宫内膜异位症患者和非子宫内膜异位症患者子宫内膜样本中 miR-34a-5p 和 VEGFA 的表达,并研究 microRNA-34a-5p 对 EnSCs 中 VEGFA 调节的潜在机制。收集有或无子宫内膜异位症患者的子宫内膜样本,采用 RT-PCR 测量两组 miR-34a-5p 的表达。从这些子宫内膜样本中分离出人子宫内膜来源的干细胞(hEnSCs),并用 miR-34a-5p 模拟物或对照 miRNA 转染 hEnSCs。qPCR 和 Western blot 用于评估 miR-34a-5p 对 hEnSCs 中 VEGFA 表达的影响,MTT 测定评估细胞生长。与无子宫内膜异位症患者相比,子宫内膜异位症患者的 miR-34a-5p 表达明显下调。与阴性对照相比,miR-34a-5p 过表达的 hEnSCs 中 VEGFA 表达水平明显降低(P<0.01)。此外,miR-34a-5p 通过靶向 VEGFA 的 3'非翻译区上调抑制 EnSCs 增殖。miR-34a-5p 为理解子宫内膜异位症的发展提供了新的途径,并可能有助于开发针对子宫内膜异位症的潜在治疗方法。

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