Circular RNA PGPEP1 induces colorectal cancer malignancy and immune escape.

Objective: Colorectal cancer (CRC) is a prevalent gastrointestinal tumor globally. Circular RNAs (circRNAs) have been identified as regulatory players in the pathogenesis of CRC. However, it is unclear whether hsa_circ_0050102 (circPGPEP1) affects the malignant progression and immune escape in CRC.

Methods: Bioinformatics analysis and circRNA in vivo precipitation experiments were performed to analyze and identify circRNAs that mediate immune escape in CRC. Using luciferase reporter assay, RIP, RNA pull-down assay, and FISH, the interaction between circPGPEP1, miR-515-5p, and nuclear factor of activated T-cell 5 (NFAT5) was identified. The functional role of circPGPEP1/miR-515-5p/NFAT5 axis in CRC anti-tumor immunity was investigated by co-culture assay, CFSE assay, and flow cytometry of CRC cells and T cells.

Results: circPGPEP1 was a stable circRNA that was highly expressed in CRC. Functionally, circPGPEP1 silencing not only effectively inhibited CRC cell proliferation, migration, EMT, and immune escape and promoted apoptosis in vitro, but also inhibited CRC tumor growth and immune escape in vivo. In terms of the regulatory mechanism, circIGF2BP3 competitively upregulated NFAT5 expression by sponging miR-515-5p. Furthermore, functional rescue experiments showed that circPGPEP1 acted in CRC by regulating the miR-515-5p/NFAT5 axis.

Conclusion: Collectively, circPGPEP1 exerts an oncogene role in CRC by regulating the miR-515-5p/NFAT5 axis.