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长链非编码RNA TUG1通过促进细胞凋亡在人类胶质瘤中发挥肿瘤抑制作用。

LncRNA TUG1 acts as a tumor suppressor in human glioma by promoting cell apoptosis.

作者信息

Li Jun, Zhang Meng, An Gang, Ma Qingfang

机构信息

Department of Neurosurgery, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou 221009, Jiangsu, China

Department of Neurosurgery, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou 221009, Jiangsu, China.

出版信息

Exp Biol Med (Maywood). 2016 Mar;241(6):644-9. doi: 10.1177/1535370215622708. Epub 2016 Jan 8.

Abstract

Previous studies have revealed multiple functional roles of long non-coding RNA taurine upregulated gene 1 in different types of malignant tumors, except for human glioma. Here, it was designed to study the potential function of taurine upregulated gene 1 in glioma pathogenesis focusing on its regulation on cell apoptosis. The expression of taurine upregulated gene 1 in glioma tissues was detected by quantitative RT-PCR and compared with that in adjacent normal tissues. Further correlation analysis was conducted to show the relationship between taurine upregulated gene 1 expression and different clinicopathologic parameters. Functional studies were performed to investigate the influence of taurine upregulated gene 1 on apoptosis and cell proliferation by using Annexin V/PI staining and cell counting kit-8 assays, respectively. And, caspase activation and Bcl-2 expression were analyzed to explore taurine upregulated gene 1-induced mechanism. taurine upregulated gene 1 expression was significantly inhibited in glioma and showed significant correlation with WHO Grade, tumor size and overall survival. Further experiments revealed that the dysregulation of taurine upregulated gene 1 affected the apoptosis and cell proliferation of glioma cells. Moreover, taurine upregulated gene 1 could induce the activation of caspase-3 and-9, with inhibited expression of Bcl-2, implying the mechanism in taurine upregulated gene 1-induced apoptosis. taurine upregulated gene 1 promoted cell apoptosis of glioma cells by activating caspase-3 and -9-mediated intrinsic pathways and inhibiting Bcl-2-mediated anti-apoptotic pathways, acting as a tumor suppressor in human glioma. This study provided new insights for the function of taurine upregulated gene 1 in cancer biology, and suggested a potent application of taurine upregulated gene 1 overexpression for glioma therapy.

摘要

以往研究揭示了长链非编码RNA牛磺酸上调基因1在除人类胶质瘤外的不同类型恶性肿瘤中的多种功能作用。在此,旨在研究牛磺酸上调基因1在胶质瘤发病机制中的潜在功能,重点关注其对细胞凋亡的调控。通过定量RT-PCR检测胶质瘤组织中牛磺酸上调基因1的表达,并与相邻正常组织中的表达进行比较。进一步进行相关性分析以显示牛磺酸上调基因1表达与不同临床病理参数之间的关系。分别使用Annexin V/PI染色和细胞计数试剂盒-8检测进行功能研究,以探讨牛磺酸上调基因1对细胞凋亡和细胞增殖的影响。并且,分析半胱天冬酶激活和Bcl-2表达以探索牛磺酸上调基因1诱导的机制。牛磺酸上调基因1的表达在胶质瘤中显著受到抑制,并且与世界卫生组织分级、肿瘤大小和总生存期显著相关。进一步的实验表明牛磺酸上调基因1的失调影响了胶质瘤细胞的凋亡和细胞增殖。此外,牛磺酸上调基因1可诱导半胱天冬酶-3和-9的激活,同时抑制Bcl-2的表达,这暗示了牛磺酸上调基因1诱导凋亡的机制。牛磺酸上调基因1通过激活半胱天冬酶-3和-9介导的内源性途径并抑制Bcl-2介导的抗凋亡途径促进胶质瘤细胞的凋亡,在人类胶质瘤中发挥肿瘤抑制作用。本研究为牛磺酸上调基因1在癌症生物学中的功能提供了新的见解,并提示牛磺酸上调基因1过表达在胶质瘤治疗中的潜在应用。

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