Objective To explore whether miR-134-3p regulates the survival and migration of colon cancer cells through targeting ADAM9/EGFR/AKT pathway. Methods Real-time qPCR was used for detecting the miR- 134-3p expression in the normal colonic epithelia (NCM460) and colon cancer cells (SW480, HCT116 and RKO). Meanwhile, Western blot was used for measuring the protein expressions of ADAM9, EGFR and AKT in these cells. Subsequently, cells were transfected with miR-134-3p mimic/miR-134-3p inhibitor, cell proliferation, apoptosis and migration were examined by CCK-8 kits, flow cytometry and Transwell migration assays, respectively. Next, the protein expressions and phosphorylation of ADAM9, EGFR and AKT were measured to evaluate the activation of ADAM9/EGFR/AKT pathway. Finally, the relationship between miR-134-3p and ADAM9 was verified with luciferase assay. Results MiR-134-3p was significantly down-regulated in the three colon cancer cells compared to the normal colonic epithelia NCM460 cells (P<0.05). In contrast, the expressions of ADAM9, EGFR and AKT increased by 2-3 folds in cancer cells compared with NCM460 cells (P <0.05). The proliferation capability of SW480 cells decreased and the count of migrated cells reduced after miR-134-3p mimic transfection. Cell apoptosis percentage elevated to (15.0±1.1)%, which was significantly higher than that of the control (9.0±1.7)% (P< 0.05). In addition, there was a significant decrease in ADAM9, p-EGFR/EGFR and p-AKT/AKT compared with the control (P<0.05). Luciferase assay confirmed that miR-134-3p could bind to ADAM9 mRNA to suppress its expression. However, miR-134-3p inhibitor showed the opposite effect against miR-134-3p mimic transfection in SW480 cells. Conclusion miR-134-3p inhibited survival and migration of colon cancer cells through targeting ADAM9 and the subsequent EGFR/AKT signaling. [ABSTRACT FROM AUTHOR]