Exosomes containing circSCP2 in colorectal cancer promote metastasis via sponging miR-92a-1-5p and interacting with PTBP1 to stabilize IGF2BP1.

Abstract

Exosomes have emerged as significant biomarkers for multiple diseases, including cancers. Circular RNAs (circRNAs), abundant in exosomes, are involved in regulating cancer development. However, the regulatory function and the underlying molecular mechanism of hsa_circ_0006906 (circSCP2) in colorectal cancer (CRC) metastasis remain unclear. A competing endogenous RNA microarray was used to analyze circRNA expression in serum exosomes in patients with CRC at early and late stages. circSCP2 expression was evaluated using qRT-PCR. The biological functions of circSCP2 in CRC were assessed through in vitro and in vivo experiments. The molecular mechanism of circSCP2 was explored using western blotting, RNA pulldown, RNA immunoprecipitation, luciferase assays, and relative rescue experiments. circSCP2 expression was significantly elevated in CRC tissues, with higher levels in serum exosomes correlating with advanced TNM stages. circSCP2 knockdown inhibited CRC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Mechanistically, circSCP2 sponged miR-92a-1-5p to increase insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) expression. Additionally, circSCP2 directly bound to and stabilized polypyrimidine tract binding protein 1 (PTBP1) by inhibiting protein ubiquitination, resulting in IGF2BP1 mRNA stabilization and enhanced CRC migration and invasion. Our findings demonstrate that circSCP2 regulates the miR-92a-1-5p/IGF2BP1 pathway, promotes PTBP1/IGF2BP1 interaction, and accelerates CRC progression. Exosomal circSCP2 is a promising circulating biomarker for CRC prognosis and needs further therapeutic investigation.