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在全反式维甲酸诱导的U87胶质瘤细胞分化过程中,长链非编码RNA与NSPc1结合并相互作用。

lncRNAs combine and crosstalk with NSPc1 in ATRA-induced differentiation of U87 glioma cells.

作者信息

Liang Zhikong, Wang Yuliang, Li Hui, Sun Yi, Gong Yanhua

机构信息

Department of Immunology, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, P.R. China.

Jiangsu Provincial Corps Hospital of Chinese People's Armed Police Force, Yangzhou 225003, P.R. China.

出版信息

Oncol Lett. 2019 Jun;17(6):5821-5829. doi: 10.3892/ol.2019.10254. Epub 2019 Apr 15.

Abstract

Nervous system polycomb 1 (NSPc1) is a member of the polycomb group (PcG) family of proteins and has been demonstrated to maintain the differentiation and pluripotency of stem cells. Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the control of pluripotency and differentiation in embryonic and pluripotent cells. In the present study, the expression levels of NSPc1 were associated with the malignant potential of various glioma cell lines. Additionally, lncRNAs were differentially expressed in glioblastoma cell lines. Following induced differentiation of U87 glioblastoma cells with all-trans retinoic acid, the expression levels of NSPc1 decreased initially, reaching its lowest point on day 6, but then subsequently increased until day 10. The expression of lncRNA candidates decreased in the cell differentiation stage. Additionally, the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), sex-determining region of the Y chromosome-box 2 overlapping transcript (SOX2OT) and antisense non-coding RNA in the INK4 locus (ANRIL) was significantly altered relative to the expression levels of NSPc1. RNA immunoprecipitation (RIP) assays demonstrated that MALAT1, SOX2OT and ANRIL bind to NSPc1 in U87 glioblastoma cells and the enrichment of ANRIL in anti-NSPc1 antibody group was associated with the expression levels of NSPc1 during U87 cell differentiation. Small interfering RNA mediated downregulation of NSPc1 expression with MALAT1, SOX2OT and ANRIL, inhibited the proliferation, and promoted apoptosis in U87 cells. The results of the present study demonstrate that MALAT1, SOX2OT and ANRIL combine and crosstalk with NSPc1 in U87 cells to affect proliferation and apoptosis.

摘要

神经系统多梳蛋白1(NSPc1)是多梳蛋白家族(PcG)的成员之一,已被证明可维持干细胞的分化和多能性。长链非编码RNA(lncRNA)已被证明参与胚胎和多能细胞中多能性和分化的调控。在本研究中,NSPc1的表达水平与各种胶质瘤细胞系的恶性潜能相关。此外,lncRNA在胶质母细胞瘤细胞系中差异表达。用全反式维甲酸诱导U87胶质母细胞瘤细胞分化后,NSPc1的表达水平最初下降,在第6天达到最低点,但随后在第10天之前又升高。lncRNA候选物的表达在细胞分化阶段降低。此外,转移相关肺腺癌转录本1(MALAT1)、Y染色体性别决定区框2重叠转录本(SOX2OT)和INK4基因座反义非编码RNA(ANRIL)的表达相对于NSPc1的表达水平有显著改变。RNA免疫沉淀(RIP)分析表明,MALAT1、SOX2OT和ANRIL在U87胶质母细胞瘤细胞中与NSPc1结合,并且在U87细胞分化过程中,抗NSPc1抗体组中ANRIL的富集与NSPc1的表达水平相关。小干扰RNA介导的NSPc1表达下调与MALAT1、SOX2OT和ANRIL共同作用,抑制了U87细胞的增殖并促进了其凋亡。本研究结果表明,MALAT1、SOX2OT和ANRIL在U87细胞中与NSPc1结合并相互作用,从而影响细胞的增殖和凋亡。

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