circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity

Circular RNAs (circRNAs) are a class of covalently closed single-stranded RNAs that have been demonstrated to involve in cancer progression. Here, we identify circNDUFB2 is downregulated in non-small cell lung cancer (NSCLC) tissues, and it negatively correlates with the malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. circNDUFB2 functions as a scaffold to enhance interaction of TRIM25 with IGF2BPs by forming a TRIM25/circNDUFB2/IGF2BPs ternary complex. The resultant ternary complex facilitates ubiquitination degradation of IGF2BPs, and N6-methyladenosine (m6A) modification of circNDUFB2 increases ubiquitination efficiency of TRIM25 for IGF2BPs. Moreover, circNDUFB2 can be recognized by RIG-I, then activates RIG-I-MAVS signaling cascades and recruits immune cells into tumor microenvironment (TME). Our data provide evidences that circNDUFB2 participates in degradation of IGF2BPs and activation of anti-tumor immunity in NSCLC progression. These findings reveal a dual-role pattern of circNDUFB2 action involved in protein ubiquitination degradation and cellular immune response. mRNA profiles in A549 cells with circNDUFB2 overexpression (circNDUFB2) versus control (Vector)