E3 ligases account for the diverse ubiquitination patterns and we confirmed that TRIM21 is an E3 ligase of NCL.[50] TRIM21, characterized by a RING domain for the E3 ubiquitin ligase, is a member of the TRIM family and plays a key role in the origin and development of cancers.[29] Subsequent mechanistic studies confirmed that circ0006646 could prevent TRIM21 from anchoring ubiquitin to NCL. Here, TRIM21 is linked to cancer.