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

LncRNA TUG1 acts as a tumor suppressor in human glioma by promoting cell apoptosis
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DOI:
10.1177/1535370215622708
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发表时间:
2016-03-01
影响因子:
3.2
通讯作者:
Ma, Qingfang
Ma, Qingfang
中科院分区:
医学4区
文献类型:
--
作者:
Li, Jun;Zhang, Meng;Ma, Qingfang

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以往的研究表明,长链非编码RNA牛磺酸上调基因1在不同类型的恶性肿瘤中发挥多种功能作用,但人脑胶质瘤除外。本研究旨在探讨牛磺酸上调基因1对胶质瘤细胞凋亡的调控作用。采用定量RT-PCR方法检测脑胶质瘤组织中牛磺酸上调基因1的表达,并与癌旁正常脑组织进行比较。进一步相关分析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。分别采用Annexin V/PI染色和细胞计数kit-8法研究牛磺酸上调基因1对细胞凋亡和细胞增殖的影响。通过检测caspase活性和Bcl-2表达,探讨牛磺酸上调gene 1表达的机制。脑胶质瘤中牛磺酸上调基因1的表达明显受到抑制,并与WHO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caspase-3和-9的激活,并抑制Bcl-2的表达,这可能是牛磺酸上调基因1诱导细胞凋亡的机制。牛磺酸上调gene 1通过激活caspase-3和caspase-9介导的内源性途径和抑制Bcl-2介导的抗凋亡途径促进胶质瘤细胞凋亡,在人脑胶质瘤中起肿瘤抑制作用。本研究为探讨牛磺酸上调基因1在肿瘤生物学中的作用提供了新的思路,并为牛磺酸上调基因1过表达治疗胶质瘤提供了可能。
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.