circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity

被引：417

作者：

Li, Botai ^{[1
]}

Zhu, Lili ^{[1
]}

Lu, Chunlai ^{[2
]}

Wang, Cun ^{[3
]}

Wang, Hui ^{[3
]}

Jin, Haojie ^{[3
]}

Ma, Xuhui ^{[3
]}

Cheng, Zhuoan ^{[1
]}

Yu, Chengtao ^{[1
]}

Wang, Siying ^{[3
]}

Zuo, Qiaozhu ^{[3
]}

Zhou, Yangyang ^{[3
]}

Wang, Jun ^{[3
]}

Yang, Chen ^{[3
]}

Lv, Yuanyuan ^{[3
]}

Jiang, Liyan ^{[4
]}

Qin, Wenxin ^{[1
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes,Sch Biome, Shanghai 200032, Peoples R China

[2] Fudan Univ, Zhongshan Hosp, Dept Thorac Surg, Shanghai 200032, Peoples R China

[3] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, Sch Med, Shanghai 200032, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Resp Med, Shanghai 200030, Peoples R China

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

中国国家自然科学基金;

关键词：

RNA-BINDING PROTEINS; CIRCULAR RNAS; DEGRADATION; EXPRESSION; RECOGNITION; WIDESPREAD; MANAGEMENT; DISTINCT; EFP;

D O I：

10.1038/s41467-020-20527-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Circular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. Mechanistically, circNDUFB2 functions as a scaffold to enhance the interaction between TRIM25 and IGF2BPs, a positive regulator of tumor progression and metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination and degradation of IGF2BPs, with this effect enhanced by N-6-methyladenosine (m(6)A) modification of circNDUFB2. Moreover, circNDUFB2 is also recognized by RIG-I to activate RIG-I-MAVS signaling cascades and recruit immune cells into the tumor microenvironment (TME). Our data thus provide evidences that circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.

引用

页数：15

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