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长链非编码 RNA FOXD2-AS1 通过 FOXD2-AS1/miR-31/CDK1 通路促进神经胶质瘤细胞周期进程和增殖。

Long noncoding RNA FOXD2-AS1 promotes glioma cell cycle progression and proliferation through the FOXD2-AS1/miR-31/CDK1 pathway.

机构信息

Department of Science and Education, The Affiliated Hospital of South-East University, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.

Department of Gastrointestinal Surgery, The Affiliated Hospital of South-East University, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.

出版信息

J Cell Biochem. 2019 Dec;120(12):19784-19795. doi: 10.1002/jcb.29284. Epub 2019 Jul 26.

Abstract

Long noncoding RNAs (lncRNAs) are vital mediators involved in cancer progression. Previous studies confirmed that FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is upregulated in tumor diseases. The potential influence of FOXD2-AS1 in glioma progression, however, remains unknown. In this paper, FOXD2-AS1 was found to be upregulated in glioma tissues. Its level was linked with glioma stage. Moreover, glioma patients expressing high level of FOXD2-AS1 suffered worse prognosis. Biological functions of FOXD2-AS1 in glioma cells were analyzed through integrative bioinformatics and TCGA RNA sequencing data analysis. Pathway enrichment analysis uncovered that FOXD2-AS1 was mainly linked with cell cycle regulation in both low-grade glioma and glioblastoma. Further experiments demonstrated that silence of FOXD2-AS1 inhibited proliferation, arrested cell cycle and downregulated cyclin-dependent kinase 1 (CDK1) in human glioma cells. Dual-luciferase reporter assay confirmed that FOXD2-AS1 upregulated CDK1 by sponging miR-31. Rescue assays were performed and confirmed the regulatory loop FOXD2-AS1/miR-31/CDK1 in glioma. Collectively, our results indicated that the FOXD2-AS1/miR-31/CDK1 axis influenced glioma progression, providing a potential new target for glioma patients.

摘要

长链非编码 RNA(lncRNAs)是参与癌症进展的重要介质。先前的研究证实,叉头框蛋白 D2 反义 RNA1(FOXD2-AS1)在肿瘤疾病中上调。然而,FOXD2-AS1 在神经胶质瘤进展中的潜在影响尚不清楚。在本文中,发现 FOXD2-AS1 在神经胶质瘤组织中上调。其水平与神经胶质瘤分期相关。此外,表达高水平 FOXD2-AS1 的神经胶质瘤患者预后较差。通过整合生物信息学和 TCGA RNA 测序数据分析分析了 FOXD2-AS1 在神经胶质瘤细胞中的生物学功能。通路富集分析表明,FOXD2-AS1 主要与低级别神经胶质瘤和胶质母细胞瘤中的细胞周期调节有关。进一步的实验表明,沉默 FOXD2-AS1 抑制了人神经胶质瘤细胞的增殖,使细胞周期停滞,并下调了细胞周期蛋白依赖性激酶 1(CDK1)。双荧光素酶报告基因实验证实,FOXD2-AS1 通过海绵 miR-31 上调 CDK1。进行了挽救实验,并证实了神经胶质瘤中 FOXD2-AS1/miR-31/CDK1 的调节环。综上所述,我们的结果表明,FOXD2-AS1/miR-31/CDK1 轴影响神经胶质瘤的进展,为神经胶质瘤患者提供了一个潜在的新靶点。

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