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.
复制标题
circNDUFB2 通过破坏 IGF2BP 的稳定性和激活抗肿瘤免疫来抑制非小细胞肺癌的进展。
DOI：
10.1038/s41467-020-20527-z
复制
发表时间：
2021-01-12
影响因子：
16.6
通讯作者：
Qin W
中科院分区：
文献类型：
--
作者：
Li B;Zhu L;Lu C;Wang C;Wang H;Jin H;Ma X;Cheng Z;Yu C;Wang S;Zuo Q;Zhou Y;Wang J;Yang C;Lv Y;Jiang L;Qin W
环状RNA（circRNA）是一类共价闭合的单链RNA，其与癌症进展有关。在这里，我们确定circNDUFB 2在非小细胞肺癌（NSCLC）组织中下调，并与NSCLC恶性特征呈负相关。circNDUFB 2升高抑制NSCLC细胞的生长和转移。从机制上讲，circNDUFB 2作为支架发挥作用，以增强TRIM 25和IGF 2BP之间的相互作用，IGF 2BP是肿瘤进展和转移的正调节因子。这种TRIM 25/circNDUFB 2/IGF 2BP三元复合物促进IGF 2BP的泛素化和降解，这种作用通过circNDUFB 2的N6-甲基腺苷（m6 A）修饰而增强。此外，circNDUFB 2还被RIG-I识别以激活RIG-I-MAVS信号级联并将免疫细胞募集到肿瘤微环境（TME）中。因此，我们的数据提供了证据表明，circNDUFB 2通过调节蛋白泛素化和降解以及细胞免疫应答，参与了NSCLC进展期间IGF 2BP的降解和抗肿瘤免疫的激活。Circular RNA（circRNA）是一类能够调控基因翻译和功能的非编码RNA。在这里，作者表明，circRNA，circNDUFB 2，在非小细胞肺癌组织中下调，并可能通过调节癌蛋白的降解和先天免疫的诱导来促进抗肿瘤免疫。
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. Circular RNAs (circRNA) is a class of non-coding RNAs that can regulate gene translation and function. Here the authors show that a circRNA, circNDUFB2, is downregulated in non-small cell lung cancer tissues, and likely contributes to anti-tumor immunity by regulating both degradation of oncoproteins and induction of innate immunity.
登录
查看更多内容
DOI：
10.1042/bj20111890
发表时间：
2012-06-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Dong XY;Fu X;Fan S;Guo P;Su D;Dong JT
通讯作者：
Dong JT
circTP63 作为 ceRNA 通过上调 FOXM1 促进肺鳞状细胞癌进展
影响因子：
16.6
作者：
Cheng, Zhuoan;Yu, Chengtao;Qin, Wenxin
通讯作者：
Qin, Wenxin
影响因子：
7.7
作者：
Dai, Ning;Ji, Fei;Avruch, Joseph
通讯作者：
Avruch, Joseph
影响因子：
8
作者：
Bell, Jessica L.;Waechter, Kristin;Muehleck, Britta;Pazaitis, Nikolaos;Koehn, Marcel;Lederer, Marcell;Huettelmaier, Stefan
通讯作者：
Huettelmaier, Stefan
影响因子：
5.9
作者：
Chan, Ying Kai;Gack, Michaela U.
通讯作者：
Gack, Michaela U.