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OBJECTIVE This study aimed to explore the possible role and mechanism of lncRNA ZEB2-AS1 in the pathogenesis of colon cancer (CCa). PATIENTS AND METHODS The expression level of ZEB2-AS1 in 41 colon cancer tissue samples and 25 normal tissues was detected by qRT-PCR, and appropriate colon cancer cell lines were screened for in vitro experiments. Subcellular localization of ZEB2-AS1 was examined. After ZEB2-AS1 was transfected into colon cancer cells by liposome method, the cell proliferation, migration ability, and cell apoptosis percentage were evaluated by CCK-8 test, transwell assay, and flow cytometry, respectively. In addition, bioinformatics was applied to detect the target genes of microRNA-188. The Luciferase gene reporter assay was then performed to analyze the relative activity of Luciferase between microRNA-188 and TAB3 or ZEB2-AS1. At the same time, the control sequence, microRNA-188 mimics, microRNA-188 mimics+ ZEB2-AS1, si-TAB3, and microRNA-188 inhibitor+ si-TAB3 were respectively transfected into cells to further verify the interaction between TAB3 and microRNA-188 or ZEB2-AS1. Besides, the glucose and lactate levels were measured to explore their roles in glycolysis. RESULTS The expression of ZEB2-AS1 in colon cancer tissues and cells was significantly higher than that in normal ones, and ZEB2-AS1 was confirmed to be mostly located in the cytoplasm. In addition, ZEB2-AS1 overexpression could enhance the cell proliferation rate and migration ability as well as reduce the cell apoptosis, which could be reversed by microRNA-188 overexpression. In addition, bioinformatics prediction and Dual-Luciferase reporter assays revealed that ZEB2-AS1 could bind to microRNA-188, which could directly target TAB3. At the same time, it was found that the overexpression of ZEB2-AS1 and low expression of microRNA-188 promoted glycolysis, while the opposite result was observed after overexpression of microRNA-188 and low expression of TAB3. CONCLUSIONS The expression of ZEB2-AS1 is significantly increased in colon cancer tissues and cells, which can promote the proliferation, migration, and promote apoptosis of colon cancer cells. It may be involved in the development of this cancer through the process of glycolysis regulated by microRNA-188/TAB3.