CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25-Mediated Ubiquitination

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide and liver metastasis is the leading reason for its mortality. Circular RNAs (circRNAs) are conclusively associated with the progression of various cancers, rendering the exploration of its specific mechanisms in colorectal cancer liver metastasis(CRLM) highly valuable. Combined with GEO (Gene Expression Omnibus) databases and clinical data in our center, we found that high expression of circSATB1 is closely related to the progression of CRLM. Functionally, circSATB1 could significantly promote the metastatic ability of CRC cells in vitro and in vivo. Mechanistically, circSATB1 facilitated the RNF25-mediated ubiquitylation and degradation of FKBP8, releasing its inhibitory effects on mTOR signaling. In this process, circSATB1 acted as a scaffold for RNF25-FKBP8 complexes. Additionally, circSATB1 could be packaged in exosomes and secreted from the CRC primary tumors into plasma. In conclusion, this study uncovered a new circSATB1 that acts as a potent promoter of CRLM and offers novel insights into the precision therapeutic strategies for CRLM.