AbstractBackground and AimColorectal cancer (CRC), the third most lethal human cancer worldwide, seriously threatens human health and life. Numerous circular RNAs (circRNAs) including circ_PLXNB1 (hsa_circ_0065378) have been confirmed to be dysregulated in CRC by RNA‐seq analysis. We aimed to explore the functional role of circ_PLXNB1 in CRC malignant behaviors and clarify its potential molecular mechanism.MethodsGene expression levels of circ_PLXNB1 and miR‐4701‐5p were determined by quantitative real‐time polymerase chain reaction analysis. MTT and Transwell assays were conducted to measure cell proliferation, invasion, and migration. Protein expression of tumor suppressor candidate 1 (TUSC1), E‐cadherin and N‐cadherin was determined by western blot analysis. Mouse xenograft models were used to investigate the role of circ_PLXNB1 in tumor growth.ResultsThe results showed that gene expression of circ_PLXNB1 in CRC tissues was significantly downregulated. Overexpression of circ_PLXNB1 inhibited the malignant behaviors of CRC cells, as manifested by the decrease in cell proliferation, cell invasion, migration, and EMT. Mechanistically, circ_PLXNB1 exerted its functional effects by binding with miR‐4701‐5p. Moreover, TUSC1 siRNA partially abolished the suppressive effect of the miR‐4701‐5p inhibitor or circ_PLXNB1 on CRC cell malignant behaviors.ConclusionsCirc_PLXNB1 attenuated CRC progression by binding with miR‐4701‐5p to overexpress TUSC1, indicating that the circ_PLXNB1/miR‐4701‐5p/TUSC1 axis might be a potential novel molecular target in CRC diagnosis and therapy.