Abundant evidence has showed that circular RNA (circRNA) plays an important role in cancer. Nonetheless, little is known about the roles and mechanisms of specific circRNAs in different cancer types. Hsa_circ_0008285 (circ_0008285), derived from the coding gene chromodomain y-like protein (CDYL), is upregulated in hepatocellular carcinoma and mantle cell lymphoma. However, we previously found, by analyzing two independent high-throughput sequencing datasets, that it was reduced in colon cancer. In this study, we explored the function and mechanism of circ_0008285 in the progression of colorectal cancer (CRC). First, the downregulated expression of circ_0008285 in CRC tissues and cell lines was confirmed using RT-qPCR analysis. In addition, the expression level of circ_0008285 was inversely correlated with tumor size, lymphatic metastasis, and tumor-node-metastasis (TNM) stage through clinicopathological parameter analysis. Functionally, knockdown of circ_0008285 promoted CRC cell proliferation and migration in vitro. Mechanistically, by using RNA-sequencing, bioinformatics analysis, dual-luciferase reporter assay, and western blotting, we determined that circ_0008285 suppressed the PI3K/AKT pathway via the miR-382-5p/PTEN axis. In conclusion, our data demonstrate a tumor suppressor role for circ_0008285 in CRC and suggest circ_0008285 as a potential target for CRC treatment. (C) 2020 Elsevier Inc. All rights reserved.