circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity.
circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity.
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DOI：
10.1038/s41467-020-20527-z
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Qin Wenxin
中科院分区：
文献类型：
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作者：
Li Botai;Zhu Lili;Lu Chunlai;Wang Cun;Wang Hui;Jin Haojie;Ma Xuhui;Cheng Zhuoan;Yu Chengtao;Wang Siying;Zuo Qiaozhu;Zhou Yangyang;Wang Jun;Yang Chen;Lv Yuanyuan;Jiang Liyan;Qin Wenxin
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-methyladenosine (mA) 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.
