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Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its angiogenic function, and its role as an oncogene has yet to be elucidated. The current study hypothesized that Ang‑2 may be an oncogene and have a function in tumor progression. An investigation of the function of Ang‑2 in the LoVo colorectal cancer (CRC) cell line in vitro, which expresses a high level of Ang‑2, was performed by knocking down endogenous expression with a targeted short hairpin RNA. The aggressive phenotypic effects of Ang‑2 on experimental and control group cells were assessed using cell proliferation, migration and invasion assays. The association between Ang‑2 expression levels and clinicopathological factors was evaluated in 415 CRC tissues using immunohistochemistry. Suppressing Ang‑2 expression decreased cellular proliferation, invasion and migration in an in vitro study. Ang‑2 overexpression was observed in 46% of patients with CRC and was significantly associated with pT (P=0.048), pN (P<0.001), venous invasion (P=0.023), lymphatic invasion (P<0.001) and tumor‑node‑metastasis stage (P=0.022). Furthermore, Ang‑2 overexpression was an independent prognostic factor in pN stages 1 and 2. These results reveal that Ang‑2 may be an oncogene in colorectal carcinogenesis and its expression may exert aggressive phenotypic effects during tumor progression. In addition, Ang‑2 expression may serve as a prognostic marker and a potential drug target. [ABSTRACT FROM AUTHOR]