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长链非编码 RNA IDH1-AS1 抑制脑胶质瘤细胞增殖和肿瘤生长。

LncRNA IDH1-AS1 suppresses cell proliferation and tumor growth in glioma.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an 710004, P.R. China.

出版信息

Biochem Cell Biol. 2020 Oct;98(5):556-564. doi: 10.1139/bcb-2019-0465. Epub 2020 Sep 29.

DOI:10.1139/bcb-2019-0465
PMID:32990028
Abstract

Glioma is a type of brain tumor that is common globally, and is associated with a variety of genetic changes. It has been reported that isocitrate dehydrogenase 1 (IDH1) is overexpressed in glioma and in HeLa cells. The lncRNA IDH1-AS1 is believed to interact with IDH1, and when IDH1-AS1 is overexpressed, HeLa cell proliferation is inhibited. However, the effects of IDH1-AS1 on glioma were relatively unknown. The results from this work show that IDH1-AS1 is downregulated in the glioma tissues. We used primary glioblastoma cell lines U251 and U87-MG to study the effects of IDH1-AS1 on glioma cell growth, in vitro and in vivo. We found that when IDH1-AS1 is overexpressed cell proliferation is inhibited, cell cycle is arrested at the G1 phase, and the protein expression levels of cyclinD1, cyclinA, cyclinE, CDK2, and CDK4 are decreased. We found that cell apoptosis was increased when IDH1-AS1 was overexpressed, as evidenced by increases in the levels of cleaved caspase-9 and -3. Conversely, knockdown of IDH1-AS1 promoted cell proliferation. Moreover, we proved that overexpression of IDH1-AS1 inhibits the tumorigenesis of U251 cells, in vivo. Furthermore, IDH1-AS1 did not affect IDH1 protein expression, but altered its enzymatic activities in glioma cells. Silencing of IDH1 reversed the effects of IDH1-AS1 upregulation on cell viability. Hence, our study provides first-hand evidence for the effects of lncRNA IDH1-AS1 on gliomas. Because overexpressing IDH1-AS1 inhibited cell growth, IDH1-AS1 could also be considered as a potential target for glioma treatment.

摘要

神经胶质瘤是一种常见的全球脑肿瘤类型,与多种遗传变化有关。据报道,异柠檬酸脱氢酶 1(IDH1)在神经胶质瘤和 HeLa 细胞中过度表达。长链非编码 RNA IDH1-AS1 被认为与 IDH1 相互作用,当 IDH1-AS1 过表达时,HeLa 细胞增殖受到抑制。然而,IDH1-AS1 对神经胶质瘤的影响相对未知。本研究结果显示,IDH1-AS1 在神经胶质瘤组织中下调。我们使用原发性神经胶质瘤细胞系 U251 和 U87-MG 研究 IDH1-AS1 对神经胶质瘤细胞生长的影响,包括体外和体内实验。我们发现,当 IDH1-AS1 过表达时,细胞增殖受到抑制,细胞周期停滞在 G1 期,细胞周期蛋白 D1、A、E、CDK2 和 CDK4 的蛋白表达水平降低。我们发现,当 IDH1-AS1 过表达时,细胞凋亡增加,证据是 cleaved caspase-9 和 -3 的水平升高。相反,IDH1-AS1 的敲低促进了细胞增殖。此外,我们证明过表达 IDH1-AS1 抑制了 U251 细胞的体内致瘤性。此外,IDH1-AS1 不影响 IDH1 蛋白表达,但改变了其在神经胶质瘤细胞中的酶活性。沉默 IDH1 逆转了 IDH1-AS1 上调对细胞活力的影响。因此,我们的研究为 lncRNA IDH1-AS1 对神经胶质瘤的影响提供了第一手证据。由于过表达 IDH1-AS1 抑制细胞生长,IDH1-AS1 也可以被认为是神经胶质瘤治疗的潜在靶点。

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