circNRIP1 impairs tumorigenesis of colorectal cancer by sponging IGF2BP1 and decreasing NACC1 mRNA stability.

BACKGROUND: Colorectal cancer (CRC) is one of the most lethal malignancies worldwide. Early diagnosis is critical in CRC treatment. More convenient and accurate biomarkers for early diagnosis are needed. However, whether circular RNAs (circRNAs) participate in colorectal tumorigenesis and their role in early diagnosis of CRC remain unknown. METHODS: We investigated the deregulated circRNAs and CRC-specific blood exosomal circRNAs in the Gene Expression Omnibus database and exoRBase. Functional assays were performed to evaluate the effects of hsa_circ_0004771 (circNRIP1) on proliferation and tumorigenesis both in vitro and in vivo. RNA pull-down, proteomic analysis, and RNA immunoprecipitation-polymerase chain reaction were performed to explore the underlying biological functions of circNRIP1 in CRC tumorigenesis. RESULTS: circNRIP1 was significantly downregulated in tumor tissues and increased in the blood exosomes of CRC patients. Knockdown of circNRIP1 significantly promoted CRC-cell proliferation and colony-forming ability in vitro and increased the tumor-formation ability in the xenograft mouse model. Mechanistically, circNRIP1 interacted with the K homology_1/2 domain of IGF2BP1 and blocked its m(6)A reader activity, and further reduced the stability of NACC1 mRNA and inhibited colorectal tumorigenesis. CONCLUSIONS: circNRIP1 is an important tumor suppressor in CRC tumorigenesis and blood exosomal circNRIP1 could be an early diagnostic biomarker for CRC.