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Long non-coding RNA PAXIP1-AS1 facilitates cell invasion and angiogenesis of glioma by recruiting transcription factor ETS1 to upregulate KIF14 expression.
Journal of Experimental & Clinical Cancer Research ( IF 11.3 ) Pub Date : 2019-12-10 , DOI: 10.1186/s13046-019-1474-7
Haiyang Xu 1 , Guifang Zhao 2, 3 , Yu Zhang 4 , Hong Jiang 5 , Weiyao Wang 3 , Donghai Zhao 3 , Hongquan Yu 1 , Ling Qi 2, 3
Affiliation  

BACKGROUND Gliomas are common life-threatening cancers, mainly due to their aggressive nature and frequent invasiveness and long non-coding RNAs (lncRNAs) are emerging as promising molecular targets. Therefore, we explored the regulatory mechanisms underlying the putative involvement of the lncRNA PAX-interacting protein 1- antisense RNA1/ETS proto-oncogene 1/kinesin family member 14 (PAXIP1-AS1/ETS1/KIF14) axis in glioma cell invasion and angiogenesis. METHODS Firstly, we identified differentially expressed lncRNA PAXIP1-AS1 as associated with glioma based on bioinformatic data. Then, validation experiments were conducted to confirm a high expression level of lncRNA PAXIP1-AS1 in glioma tissues and cells, accompanied by upregulated KIF14. We further examined the binding between lncRNA PAXIP1-AS1, KIF14 promoter activity, and transcription factor ETS1. Next, overexpression vectors and shRNAs were delivered to alter the expression of lncRNA PAXIP1-AS1, KIF14, and ETS1 to analyze their effects on glioma progression in vivo and in vitro. RESULTS LncRNA PAXIP1-AS1 was mainly distributed in the nucleus of glioma cells. LncRNA PAXIP1-AS1 could upregulate the KIF14 promoter activity by recruiting transcription factor ETS1. Overexpression of lncRNA PAXIP1-AS1 enhanced migration, invasion, and angiogenesis of human umbilical vein endothelial cells in glioma by recruiting the transcription factor ETS1 to upregulate the expression of KIF14, which was further confirmed by accelerated tumor growth in nude mice. CONCLUSIONS The key findings of this study highlighted the potential of the lncRNA PAXIP1-AS1/ETS1/KIF14 axis as a therapeutic target for glioma treatment, due to its role in controlling the migration and invasion of glioma cells and its angiogenesis.

中文翻译:

长的非编码RNA PAXIP1-AS1通过募集转录因子ETS1来上调KIF14表达,从而促进神经胶质瘤的细胞侵袭和血管生成。

背景技术神经胶质瘤是常见的威胁生命的癌症,这主要是由于它们的侵袭性和频繁的侵袭性,长的非编码RNA(lncRNA)逐渐成为有希望的分子靶标。因此,我们探讨了神经胶质瘤细胞侵袭和血管生成中lncRNA PAX相互作用蛋白1-反义RNA1 / ETS原癌基因1 /驱动蛋白家族成员14(PAXIP1-AS1 / ETS1 / KIF14)轴假定参与的调控机制。方法首先,我们根据生物信息学数据鉴定出差异表达的lncRNA PAXIP1-AS1与神经胶质瘤有关。然后,进行验证实验,以确认在胶质瘤组织和细胞中lncRNA PAXIP1-AS1的高表达水平,并伴有上调的KIF14。我们进一步检查了lncRNA PAXIP1-AS1,KIF14启动子活性之间的结合,和转录因子ETS1。接下来,递送过表达载体和shRNA,以改变lncRNA PAXIP1-AS1,KIF14和ETS1的表达,以分析它们对体内外胶质瘤进展的影响。结果LncRNA PAXIP1-AS1主要分布在神经胶质瘤细胞核中。LncRNA PAXIP1-AS1可以通过募集转录因子ETS1来上调KIF14启动子的活性。lncRNA PAXIP1-AS1的过表达通过募集转录因子ETS1来上调KIF14的表达,从而增强了神经胶质瘤中人脐静脉内皮细胞的迁移,侵袭和血管生成,这一点在裸鼠体内肿瘤的加速生长中得到了进一步证实。结论这项研究的主要发现强调了lncRNA PAXIP1-AS1 / ETS1 / KIF14轴作为神经胶质瘤治疗靶点的潜力,
更新日期:2019-12-10
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