HOTAIRM1调节OCT4表达维持胶质瘤干细胞的自我更新

基础医学与临床 ›› 2019, Vol. 39 ›› Issue (6): 792-797.

HOTAIRM1调节OCT4表达维持胶质瘤干细胞的自我更新

王珊珊¹,彭小忠²,韩为³

1. 中国医学科学院基础医学研究所
2. 中国医学科学院基础医学研究所北京协和医学院基础学院医学分子生物学国家重点实验室
3. 中国医学科学院基础医学研究所北京协和医学院基础学院

收稿日期:2019-01-28 修回日期:2019-04-16 出版日期:2019-06-05 发布日期:2019-06-04
通讯作者: 韩为 E-mail:hanweijx2002@163.com
基金资助:
国家自然科学基金

HOTAIRM1 maintains self-renewal of glioma stem cells by modulating OCT4 expression

Xiao-zhong PENGWei HAN²

Received:2019-01-28 Revised:2019-04-16 Online:2019-06-05 Published:2019-06-04
Contact: Wei HAN E-mail:hanweijx2002@163.com

摘要/Abstract

摘要： 目的探究粒细胞特异表达的HOXA转录本反义RNA 1（HOTAIRM1）在胶质瘤干细胞中发挥的功能及分子机制。方法 Real-time PCR检测HOTAIRM1在胶质瘤干细胞中的表达谱；肿瘤球形成实验和有限稀释实验检测过表达或敲低HOTAIRM1后胶质瘤干细胞自我更新能力；Real-time PCR和Western blot检测干性标志物的表达；双荧光素酶报告基因实验检测OCT4启动子活性。全反式维甲酸（ATRA）处理NB4急性早幼粒细胞白血病细胞和胶质瘤干细胞GSC2后检测HOTAIRM1表达。结果与对照组相比，过表达HOTAIRM1的胶质瘤干细胞自我更新能力呈显著上升（P<0.05）；干性标志物NESTIN、OCT4及SOX2表达增加（P<0.05）。敲低HOTAIRM1结果相反。过表达HOTAIRM1可促进OCT4启动子转录活性（P<0.05）。ATRA处理GSC2后HOTAIRM1表达下调（P<0.01）。结论 HOTAIRM1通过调节OCT4表达维持胶质瘤干细胞的自我更新。

关键词: 胶质瘤干细胞, HOTAIRM1, OCT4, 自我更新

Abstract: Objective To explore the function and molecular mechanism of HOXA transcript antisense RNA (myeloid-specific 1, HOTAIRM1) in glioma stem cells. Methods Real-time PCR detected the expression profile of HOTAIRM1 in glioma stem cells; Tumor spheroid formation assay and limiting dilution assay were used to detect the ability of self-renewal of tumor stem cells after HOTAIRM1 overexpression or knockdown; Real time PCR and Western blot were used to detect the expression of stemness markers; Dual-luciferase reporter gene assay was used to detect the effect of HOTAIRM1 on the activity of OCT4 promoter; All-trans retinoic acid (ATRA) was used to treat NB4 acute promyelocytic leukemia cells and glioma stem cells GSC2. Results Compared with the control group, the self-renewal ability of glioma stem cells overexpressing HOTAIRM1 was significantly enhanced (P<0.05); Western blot showed up-regulation of the stemness markers(P<0.05). The results of knocking down HOTAIRM1 were opposite. Overexpression of HOTAIRM1 promoted the transcriptional activity of the OCT4 promoter. The expression of HOTAIRM1 was down-regulated after ATRA treatment of GSC2. Conclusions HOTAIRM1 maintains self-renewal of glioma stem cells by modulating OCT4 expression.

Key words: Glioma stem cells, HOTAIRM1, OCT4, Self-renewal

中图分类号:

Q527

王珊珊彭小忠韩为. HOTAIRM1调节OCT4表达维持胶质瘤干细胞的自我更新[J]. 基础医学与临床, 2019, 39(6): 792-797.

Xiao-zhong PENG Wei HAN. HOTAIRM1 maintains self-renewal of glioma stem cells by modulating OCT4 expression[J]. Basic & Clinical Medicine, 2019, 39(6): 792-797.

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[9]	姜开军王菊周宗瑶. 胚胎干细胞增殖分化相关基因[J]. 基础医学与临床, 2008, 28(3): 294-296.