lncRNA NEAT1 在子宫内膜异位症中的表达及其在异位子宫内膜细胞中通过 miR-124-3p 介导的生物学功能。
Expression of lncRNA NEAT1 in endometriosis and its biological functions in ectopic endometrial cells as mediated via miR-124-3p.
机构信息
Department of Obstetrics and Gynecology, Taizhou People's Hospital Affiliated to Nantong University, 399 Hailing Road, Taizhou, 225300, People's Republic of China.
Department of Operation, Taizhou People's Hospital Affiliated to Nantong University, Taizhou, 225300, China.
出版信息
Genes Genomics. 2022 May;44(5):527-537. doi: 10.1007/s13258-021-01184-y. Epub 2022 Jan 30.
BACKGROUND
Endometriosis (EM) is a gynecological disease that poses severe health risks to women, although its pathogenesis has yet to be fully elucidated. It has been shown that long non-coding RNAs (lncRNAs) are closely associated with EM initiation and have a role in the development of this disease. Previous studies exploring the expression of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) have shown that this lncRNA functions as a tumor promoter in endometrial cancer. However, its exact mechanism of action in EM remains unclear.
OBJECTIVE
This report was designed to illustrate the potential molecular mechanisms of lncRNA NEAT1 on EM.
METHODS
Endometrial tissues were extracted from EM model rats and patients with EM. Hematoxylin and eosin staining was applied to detect the morphological changes that occurred in rats after construction of the model. Endometrial stromal cells (ESCs) were extracted from either ectopic endometrium (EC) or eutopic endometrium (EU) tissues from patients with EM. LncRNA NEAT1 and miR-124-3p expression in EM tissues and cells were subsequently evaluated by reverse transcription-quantitative (RT-q)PCR analysis. MTT assay, flow cytometric analysis, western blot assay and Transwell assay were then employed to examine the effect of NEAT1 and miR-124-3p on EC-ESC proliferation, apoptosis, migration and invasion, respectively. The targeted relationship between lncRNA NEAT1 and miR-124-3p was subsequently confirmed by dual-luciferase and co-transfection assays.
RESULTS
MiR-124-3p was identified as a target of NEAT1, and could be negatively regulated by NEAT1 in EC-ESCs. The expression level of NEAT1 was evidently increased, whereas that of miR-124-3p was decreased, in the EM in vivo model, EM tissues and EC-ESCs from patients with EM. The loss-of-function assays further established that silencing of NEAT1 could inhibit EC-ESC proliferation, migration, and invasion, but it led to the promotion of apoptosis via targeting miR-124-3p.
CONCLUSIONS
NEAT1 is significantly upregulated in EM, promoting malignant behavior in EM through targeting miR-124-3p expression.
背景
子宫内膜异位症（EM）是一种对女性健康构成严重威胁的妇科疾病，尽管其发病机制尚未完全阐明。已经表明，长链非编码 RNA（lncRNA）与 EM 的发生密切相关，并在该疾病的发展中发挥作用。先前研究探索核斑蛋白组装转录物 1（NEAT1）的 lncRNA 表达表明，这种 lncRNA 在子宫内膜癌中作为肿瘤促进剂发挥作用。然而，其在 EM 中的确切作用机制尚不清楚。
目的
本报告旨在阐述 lncRNA NEAT1 在 EM 中的潜在分子机制。
方法
从 EM 模型大鼠和 EM 患者中提取子宫内膜组织。苏木精和伊红染色用于检测大鼠模型构建后发生的形态学变化。从 EM 患者的异位内膜（EC）或在位内膜（EU）组织中提取子宫内膜基质细胞（ESC）。通过逆转录定量（RT-q）PCR 分析评估 EM 组织和细胞中 lncRNA NEAT1 和 miR-124-3p 的表达。然后，采用 MTT 分析、流式细胞术分析、western blot 分析和 Transwell 分析分别检测 NEAT1 和 miR-124-3p 对 EC-ESC 增殖、凋亡、迁移和侵袭的影响。通过双荧光素酶和共转染实验进一步证实 lncRNA NEAT1 与 miR-124-3p 的靶向关系。
结果
miR-124-3p 被鉴定为 NEAT1 的靶标，并且可以在 EC-ESCs 中被 NEAT1 负调控。在体内 EM 模型、EM 组织和 EM 患者的 EC-ESCs 中，NEAT1 的表达水平明显升高，而 miR-124-3p 的表达水平降低。失活功能试验进一步证实，沉默 NEAT1 可通过靶向 miR-124-3p 抑制 EC-ESC 增殖、迁移和侵袭，但通过靶向 miR-124-3p 促进凋亡。
结论
在 EM 中，NEAT1 显著上调，通过靶向 miR-124-3p 表达促进 EM 中的恶性行为。
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