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长链非编码RNA NBAT1通过miR-21/SOX7轴抑制胶质瘤进展。

Long non-coding RNA NBAT1 inhibits the progression of glioma through the miR-21/SOX7 axis.

作者信息

Guan Ning, Wang Rui, Feng Xu, Li Chenguang, Guo Wenshi

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.

出版信息

Oncol Lett. 2020 Sep;20(3):3024-3034. doi: 10.3892/ol.2020.11847. Epub 2020 Jul 9.

Abstract

Glioma is one of the most prevalent types of malignancy in the central nervous system worldwide, and the prognosis of patients with late stage glioma remains poor. Thus, the development of promising therapeutic strategies against glioma is essential. Long non-coding RNAs (lncRNAs) are functional RNA molecules involved in the initiation and progression of tumors, including glioma. Investigation on the regulatory roles of lncRNAs may facilitate the development of effective treatments. lncRNA NBAT1 is associated with the growth and metastasis of cancer; however, its underlying molecular mechanisms remain unknown. Thus, the present study aimed to investigate the effects of NBAT1 in glioma. The expression levels of NBAT1, microRNA (miRNA/miR)-21 and SOX7 in patients with glioma, and healthy donors using reverse transcription-quantitative PCR analysis. Human glioma cells (A172 and AM138) and normal astrocytes were used to establish the NBAT1-knockdown and overexpression models. Cell Counting Kit-8 and Transwell assays were performed to determine whether NBAT1 exerted effects on cell proliferation, migration and invasion. The results demonstrated that NBAT1 expression decreased in glioma tissues compared to normal samples. Additionally, downregulation of NBAT1 was detected in human glioma cells compared with normal astrocytes. Overexpression of NBAT1 inhibited glioma cell proliferation, migration and invasion. In addition, miR-21 was identified as a potential target of NBAT1, and the effects of miR-21-induced cell proliferation and metastasis were reversed following overexpression of NBAT1. Furthermore, SOX7 was predicted as the potential target of miR-21, and its expression was upregulated in glioma cells by overexpression of NBAT1 compared with the vehicle only control. Taken together, the results of the present study provide novel insight into the functions of NBAT1 in glioma, suggesting that the NBAT1/miR-21/SOX7 axis may act as a potential therapeutic target for the treatment of patients with glioma.

摘要

胶质瘤是全球中枢神经系统中最常见的恶性肿瘤类型之一,晚期胶质瘤患者的预后仍然很差。因此,开发有前景的抗胶质瘤治疗策略至关重要。长链非编码RNA(lncRNA)是参与肿瘤发生和发展的功能性RNA分子,包括胶质瘤。对lncRNA调控作用的研究可能有助于开发有效的治疗方法。lncRNA NBAT1与癌症的生长和转移有关;然而,其潜在的分子机制仍然未知。因此,本研究旨在探讨NBAT1在胶质瘤中的作用。采用逆转录定量PCR分析胶质瘤患者和健康供体中NBAT1、微小RNA(miRNA/miR)-21和SOX7的表达水平。使用人胶质瘤细胞(A172和AM138)和正常星形胶质细胞建立NBAT1敲低和过表达模型。进行细胞计数试剂盒-8和Transwell实验以确定NBAT1是否对细胞增殖、迁移和侵袭有影响。结果表明,与正常样本相比,胶质瘤组织中NBAT1表达降低。此外,与正常星形胶质细胞相比,在人胶质瘤细胞中检测到NBAT1下调。NBAT1的过表达抑制了胶质瘤细胞的增殖、迁移和侵袭。此外,miR-21被鉴定为NBAT1的潜在靶点,NBAT1过表达后,miR-21诱导的细胞增殖和转移作用被逆转。此外,SOX7被预测为miR-21的潜在靶点,与仅载体对照相比,NBAT1过表达使胶质瘤细胞中SOX7的表达上调。综上所述,本研究结果为NBAT1在胶质瘤中的功能提供了新的见解,表明NBAT1/miR-21/SOX7轴可能作为治疗胶质瘤患者的潜在治疗靶点。

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