METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling

被引：29

作者：

Yin, Jianxing ^{[1
]}

Ding, Fangshu ^{[2
,3
]}

Cheng, Zhangchun ^{[4
]}

Ge, Xin ^{[2
,3
]}

Li, Yanhui ^{[2
,3
]}

Zeng, Ailiang ^{[5
]}

Zhang, Junxia ^{[4
]}

Yan, Wei ^{[4
]}

Shi, Zhumei ^{[4
]}

Qian, Xu ^{[2
,3
,6
]}

You, Yongping ^{[4
]}

Ding, Zhiliang ^{[1
]}

Ji, Jing ^{[1
,4
]}

Wang, Xiefeng ^{[4
]}

机构：

[1] Nanjing Med Univ, Affiliated Suzhou Hosp, Suzhou Municipal Hosp, Gusu Sch, Suzhou 215006, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Inst Brain Tumors, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatmen, Nanjing 211166, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Nutr & Food Hyg, Nanjing 211166, Jiangsu, Peoples R China

[4] Nanjing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Nanjing 210029, Jiangsu, Peoples R China

[5] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX USA

[6] Nanjing Med Univ, Canc Hosp, Affiliated Canc Hosp, Jiangsu Inst Canc Res, Nanjing 210009, Jiangsu, Peoples R China

来源：

CELL DEATH & DISEASE | 2023年 / 14卷 / 07期

关键词：

GLIOBLASTOMA; EXPRESSION; PROLIFERATION; CANCER; RNAS;

D O I：

10.1038/s41419-023-05933-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Long noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) are essential for tumor initiation, maintenance, and therapeutic resistance. However, the biological functions and underlying mechanisms of lncRNAs in GSCs remain poorly understood. Here, we identified that LINC00839 was overexpressed in GSCs. A high level of LINC00839 was associated with GBM progression and radiation resistance. METTL3-mediated m6A modification on LINC00839 enhanced its expression in a YTHDF2-dependent manner. Mechanistically, LINC00839 functioned as a scaffold promoting c-Src-mediated phosphorylation of & beta;-catenin, thereby inducing Wnt/& beta;-catenin activation. Combinational use of celecoxib, an inhibitor of Wnt/& beta;-catenin signaling, greatly sensitized GSCs to radiation. Taken together, our results showed that LINC00839, modified by METTL3-mediated m6A, exerts tumor progression and radiation resistance by activating Wnt/& beta;-catenin signaling.

引用

页数：12

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