lncRNA LINC00665 Stabilized by TAF15 Impeded the Malignant Biological Behaviors of Glioma Cells via STAU1-Mediated mRNA Degradation

被引：55

作者：

Ruan, Xuelei ^{[1
,2
,3
]}

Zheng, Jian ^{[4
,5
,6
]}

Liu, Xiaobai ^{[4
,5
,6
]}

Liu, Yunhui ^{[4
,5
,6
]}

Liu, Libo ^{[1
,2
,3
]}

Ma, Jun ^{[1
,2
,3
]}

He, Qianru ^{[1
,2
,3
]}

Yang, Chunqing ^{[4
,5
,6
]}

Wang, Di ^{[4
,5
,6
]}

Cai, Heng ^{[4
,5
,6
]}

Li, Zhen ^{[4
,5
,6
]}

Liu, Jing ^{[4
,5
,6
]}

Xue, Yixue ^{[1
,2
,3
]}

机构：

[1] China Med Univ, Sch Life Sci, Dept Neurobiol, Shenyang 110122, Peoples R China

[2] China Med Univ, Key Lab Cell Biol, Minist Publ Hlth China, Shenyang 110122, Peoples R China

[3] China Med Univ, Key Lab Med Cell Biol, Minist Educ China, Shenyang 110122, Peoples R China

[4] China Med Univ, Dept Neurosurg, Shengjing Hosp, Shenyang 110004, Peoples R China

[5] Liaoning Clin Med Res Ctr Nervous Syst Dis, Shenyang 110004, Peoples R China

[6] Key Lab Neurooncol Liaoning Prov, Shenyang 110004, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2020年 / 20卷

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

TRANSCRIPTION FACTOR-I; COMPETITIVELY BINDING; CANCER PROGRESSION; UP-REGULATION; EXPRESSION; DECAY; PROLIFERATION; HUR; INDUCTION; PROTEINS;

D O I：

10.1016/j.omtn.2020.05.003

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Glioma is a brain cancer characterized by strong invasiveness with limited treatment options and poor prognosis. Recently, dysregulation of long non-coding RNAs (lncRNAs) has emerged as an important component in cellular processes and tumorigenesis. In this study, we demonstrated that TATA-box binding protein associated factor 15 (TAF15) and long intergenic non-protein coding RNA 665 (LINC00665) were both downregulated in glioma tissues and cells. TAF15 overexpression enhanced the stability of LINC00665, inhibiting malignant biological behaviors of glioma cells. Both metal regulatory transcription factor 1 (MTF1) and YY2 transcription factor (YY2) showed high expression levels in glioma tissues and cells, and their knockdown inhibited malignant progression. Mechanistically, overexpression of LINC00665 was confirmed to destabilize MTF1 and YY2 mRNA by interacting with STAU1, and knockdown of STAU1 could rescue the MTF1 and YY2 mRNA degradation caused by LINC00665 overexpression. G2 and S-phase expressed 1 (GTSE1) was identified as an oncogene in glioma, and knockdown of MTF1 or YY2 decreased the mRNA and protein expression levels of GTSE1 through direct binding to the GTSE1 promoter region. Our study highlights a key role of the TAF15/LINC00665/MTF1(YY2)/GTSE1 axis in modulating the malignant biological behaviors of glioma cells, suggesting novel mechanisms by which lncRNAs affect STAU1-mediated mRNA stability, which can inform new molecular therapies for glioma.

引用

页码：823 / 840

页数：18

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