癌症研究
泛素
肿瘤进展
转移
免疫系统
肺癌
肿瘤微环境
免疫
调节器
生物
癌症
化学
细胞生物学
医学
下调和上调
免疫学
内科学
生物化学
基因
遗传学
作者
Botai Li,Lili Zhu,Lu Chen,Cun Wang,Hui Wang,Haojie Jin,Xuhui Ma,Zhuoan Cheng,Caoyang Yu,Siying Wang,Qiaozhu Zuo,Yangyang Zhou,Jun Wang,Chen Yang,Yuanyuan Lv,Liyan Jiang,Wenxin Qin
标识
DOI:10.1038/s41467-020-20527-z
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 N6-methyladenosine (m6A) 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.
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