circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity.
Botai LiLili ZhuChunlai LuCun WangHui WangHaojie JinXuhui MaZhuoan ChengChengtao YuSiying WangQiaozhu ZuoYangyang ZhouJun WangChen YangYuanyuan LvLiyan JiangWenxin QinPublished in: Nature communications (2021)
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.
Keyphrases
- binding protein
- small cell lung cancer
- pi k akt
- advanced non small cell lung cancer
- growth hormone
- immune response
- signaling pathway
- cell cycle arrest
- induced apoptosis
- brain metastases
- gene expression
- poor prognosis
- electronic health record
- transcription factor
- cell proliferation
- young adults
- gold nanoparticles
- inflammatory response
- dendritic cells
- big data
- protein protein
- endoplasmic reticulum stress
- data analysis