Yu Wei, Xiang Dulei, Jia Houjun, He Xin, Sheng Jie, Long Yuxiang, Zhu Shujuan, Wang Kejian, Liu Qian
Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Cancer Manag Res. 2020 Feb 13;12:1151-1161. doi: 10.2147/CMAR.S227327. eCollection 2020.
Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) are deregulated in many cancers and exert their functions through multiple cancer-related biological processes. Glioma is the most common primary malignant central nervous system tumor and has a high fatality rate in adults. In current study, we aimed to determine the role and functional mechanism of the lncRNA BCYRN1 in glioma.
Gain-of-function and loss-of function approaches were used to investigate the function of BCYRN1. The effects of BCYRN1 on glioma cell proliferation, migration and invasion were evaluated using MTS, Transwell and wound-healing assays. The correlation between the expression of BCYRN1 and miR-125a-5p was verified by quantitative real-time PCR.
The upregulation of BCYRN1 promoted the proliferation, migration and invasion of glioma cells. Meanwhile, the knockdown of BCYRN1 had the opposite effects. BCYRN1 was negatively correlated with miR-125a-5p. Additionally, TAZ, the endogenous target of miR-125a-5p, could be regulated by BCYRN1 in RNA and protein levels. A miR-125a-5p inhibitor restored BCYRN1 siRNA function in glioma.
The present study indicates that BCYRN1 promotes glioma cell proliferation, invasion and migration in vitro. Mechanistically, upregulated expression of BCYRN1 in glioma acts as a sponge to sequester the endogenous tumor suppressor miR-125a-5p and to further increase the expression TAZ. Our findings suggest that BCYRN1 is a novel oncogene and a new therapeutic target for glioma.
大量研究表明，长链非编码RNA（lncRNA）在许多癌症中表达失调，并通过多种与癌症相关的生物学过程发挥作用。胶质瘤是最常见的原发性恶性中枢神经系统肿瘤，在成年人中死亡率很高。在本研究中，我们旨在确定lncRNA BCYRN1在胶质瘤中的作用和功能机制。
采用功能获得和功能缺失方法研究BCYRN1的功能。使用MTS、Transwell和伤口愈合试验评估BCYRN1对胶质瘤细胞增殖、迁移和侵袭的影响。通过定量实时PCR验证BCYRN1与miR-125a-5p表达之间的相关性。
BCYRN1的上调促进了胶质瘤细胞的增殖、迁移和侵袭。同时，敲低BCYRN1则产生相反的效果。BCYRN1与miR-125a-5p呈负相关。此外，miR-125a-5p的内源性靶标TAZ在RNA和蛋白质水平上可受BCYRN1调控。miR-125a-5p抑制剂可恢复BCYRN1 siRNA在胶质瘤中的功能。
本研究表明，BCYRN1在体外促进胶质瘤细胞增殖、侵袭和迁移。机制上，胶质瘤中BCYRN1表达上调起到海绵作用，隔离内源性肿瘤抑制因子miR-125a-5p，并进一步增加TAZ的表达。我们的研究结果表明，BCYRN1是一种新型癌基因，也是胶质瘤的一个新的治疗靶点。
