circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity
العنوان: | circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity |
---|---|
المؤلفون: | Jun Wang, Chengtao Yu, Haojie Jin, Chunlai Lu, Zhuoan Cheng, Lili Zhu, Qiaozhu Zuo, Wenxin Qin, Yangyang Zhou, Siying Wang, Hui Wang, Liyan Jiang, Botai Li, Yuanyuan Lv, Cun Wang, Chen Yang, Xuhui Ma |
المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications |
بيانات النشر: | Springer Science and Business Media LLC, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 0301 basic medicine, Lung Neoplasms, Ubiquitylation, General Physics and Astronomy, Metastasis, Tripartite Motif Proteins, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Receptors, Immunologic, Mice, Inbred BALB C, Multidisciplinary, Protein Stability, Chemistry, RNA-Binding Proteins, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Disease Progression, Tumour immunology, DEAD Box Protein 58, Female, Protein Binding, Proteasome Endopeptidase Complex, TRIM25, Ubiquitin-Protein Ligases, Science, Down-Regulation, Mice, Nude, Models, Biological, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Immune system, medicine, Animals, Humans, RNA, Messenger, Cell Proliferation, Tumor microenvironment, Ubiquitin, Cell growth, Ubiquitination, Cancer, RNA, Circular, General Chemistry, medicine.disease, Protein ubiquitination, 030104 developmental biology, Tumor progression, Proteolysis, Cancer research, RNA, Non-small-cell lung cancer, Transcription Factors |
الوصف: | 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. |
تدمد: | 2041-1723 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::070356570de993dffdd3a4f97bdd7f80 https://doi.org/10.1038/s41467-020-20527-z |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....070356570de993dffdd3a4f97bdd7f80 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20411723 |
---|