Background and Aims Circular RNA circRAD18 has been found to play a promoting role in the progression of breast cancer and thyroid cancer, but its expression and function in other malignant tumors have not been fully elucidated. In our previous study, we used bioinformatics software to predict that circRAD18 can interact with miR-516b through complementary binding, and pyruvate dehydrogenase kinase 1 (PDK1), a key regulator of glucose metabolism, may a target gene of miR-516b. Therefore, this study was conducted to preliminarily investigate the expression and function of circRAD18 in colorectal cancer cells and its regulatory relationship with the target miRNA and downstream target genes.Methods The expression of circRAD18 in different colorectal cancer cell lines (SW480, SW620, HT-29) and normal colorectal epithelial cells (NCM460) was detected using qRT-PCR. After silencing circRAD18 with si-circRAD18 in colorectal cancer cells, cell proliferation, glucose uptake, and lactate production were assessed using CCK-8 assay and corresponding kits. The binding relationship between circRAD18, miR-516b, and PDK1 was analyzed through dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) experiment. Finally, overexpression and knockdown experiments were conducted to further validate the relationships among them.Results Compared to normal colorectal epithelial cells, circRAD18 was significantly upregulated in all colorectal cancer cell lines (all P<0.05). Transfection with si-circRAD18 resulted in a significant decrease in colorectal cancer cell proliferation, glucose uptake, and lactate production (all P<0.05). Dual-luciferase reporter gene assay and RIP experiments confirmed the binding of circRAD18 to miR-516b, and PDK1 was identified as a downstream target gene of miR-516b. Transfection with miR-516b mimic or si-circRAD18 significantly inhibited cellular glucose uptake, lactate production, and PDK1 protein expression in colorectal cancer cells, and the supplementation of PDK1 could reverse this inhibitory effect (all P<0.05).Conclusions CircRAD18 is upregulated in colorectal cancer cells and is closely associated with enhanced cell proliferation. The underlying mechanism may involve circRAD18 adsorbing miR-516b through sponge uptake, leading to upregulation of PDK1 expression, and subsequently, reprogramming of glucose metabolism in colorectal cancer cells.