Circ Drives Gastric Cancer Progression Through Suppressing Degradation Via Interacting with UCHL3

Our previous study has reported that metastasis-associated protein 2 () plays essential roles in tumorigenesis and aggressiveness of gastric cancer (GC). However, the underlying molecular mechanisms of -mediated GC and its upstream regulation mechanism remain elusive. In this study, we identified a novel circular RNA (circRNA) generated from the gene (circ) as a crucial regulator in GC progression. Circ was highly expressed in GC tissues and cell lines, and circ promoted the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Mechanistically, circ interacted with ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) to restrain ubiquitination and stabilize protein expression, thereby facilitating tumor progression. Moreover, circ was mainly encapsulated and transported by exosomes to promote GC cell progression. Taken together, these findings uncover that circ suppresses degradation by interacting with UCHL3, thereby promoting GC progression. In conclusion, we identified a cancer-promoting axis (circ/UCHL3/) in GC progression, which paves the way for us to design and synthesize targeted inhibitors as well as combination therapies.