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下调lncRNA NEAT1的表达通过调节视网膜母细胞瘤细胞中的miR-24-3p/LRG1轴来抑制细胞迁移、侵袭和上皮-间质转化。

Knockdown of lncRNA NEAT1 expression inhibits cell migration, invasion and EMT by regulating the miR-24-3p/LRG1 axis in retinoblastoma cells.

作者信息

Luan Lan, Hu Qiang, Wang Yan, Lu Lu, Ling Jiaojiao

机构信息

Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.

出版信息

Exp Ther Med. 2021 Apr;21(4):367. doi: 10.3892/etm.2021.9798. Epub 2021 Feb 18.

Abstract

Retinoblastoma (RB) is the most common primary intraocular cancer type that occurs during retinal development in childhood. Previous studies have reported that long non-coding RNAs (lncRNAs) are involved in the development of RB. Therefore, the aim of the present study was to investigate the effects and underlying regulatory mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in RB. The expression levels of NEAT1, microRNA (miR)-24-3p and leucine-rich-α-2-glycoprotein (LRG1) were detected using reverse transcription-quantitative PCR (RT-qPCR). Moreover, the protein expression levels of LRG1, matrix metalloproteinase 9, N-cadherin and E-cadherin were detected via western blotting. Furthermore, cell migration and invasion abilities were evaluated via Transwell assays. The targeting relationships between miR-24-3p and NEAT1 or LRG1 were predicted using online software and confirmed via dual-luciferase reporter assay. In the present study, NEAT1 and LRG1 were upregulated, and miR-24-3p was downregulated in RB tissues and cells compared with the corresponding healthy tissues and cells. Moreover, miR-24-3p was identified as a target of NEAT and LRG1 was demonstrated to be a direct target gene of miR-24-3p. Knockdown of NEAT1 or LRG1 significantly suppressed RB cell migration and invasion ability, while the effects were reversed by an miR-24-3p inhibitor. In addition, the downregulation of LRG1 caused by miR-24-3p was restored following the overexpression of NEAT1 in RB cells. It was also demonstrated that NEAT1 knockdown inhibited the epithelial-to-mesenchymal transition (EMT) pathway by inhibiting the expression of LRG via targeting miR-24-3p. In conclusion, the present results suggest that silencing of NEAT1 suppresses cell migration, invasion and the EMT process by downregulating LRG1 expression via sponging miR-24-3p in RB, thus indicating that NEAT1 may be a potential candidate for RB treatment.

摘要

视网膜母细胞瘤(RB)是儿童视网膜发育过程中最常见的原发性眼内癌类型。先前的研究报道长链非编码RNA(lncRNA)参与了RB的发生发展。因此,本研究旨在探讨核旁斑组装转录本1(NEAT1)在RB中的作用及潜在调控机制。采用逆转录定量PCR(RT-qPCR)检测NEAT1、微小RNA(miR)-24-3p和富含亮氨酸α-2糖蛋白(LRG1)的表达水平。此外,通过蛋白质印迹法检测LRG1、基质金属蛋白酶9、N-钙黏蛋白和E-钙黏蛋白的蛋白表达水平。进一步通过Transwell实验评估细胞迁移和侵袭能力。使用在线软件预测miR-24-3p与NEAT1或LRG1之间的靶向关系,并通过双荧光素酶报告基因实验进行验证。在本研究中,与相应的健康组织和细胞相比,RB组织和细胞中NEAT1和LRG1上调,而miR-24-3p下调。此外,miR-24-3p被鉴定为NEAT1的靶标,LRG1被证明是miR-24-3p的直接靶基因。敲低NEAT1或LRG1可显著抑制RB细胞的迁移和侵袭能力,而miR-24-3p抑制剂可逆转这些作用。此外,RB细胞中过表达NEAT1后,miR-24-3p导致的LRG1下调得以恢复。还证明敲低NEAT1通过靶向miR-24-3p抑制LRG1的表达,从而抑制上皮-间质转化(EMT)途径。总之,本研究结果表明,沉默NEAT1通过在RB中海绵化miR-24-3p下调LRG1表达,从而抑制细胞迁移、侵袭和EMT过程,表明NEAT1可能是RB治疗的潜在候选靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dd0/7903428/417bba5d1fca/etm-21-04-09798-g00.jpg

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