Abstract: Background: Dicer is a multidomain ribonuclease III enzyme involved in the biogenesis of microRNAs (miRNAs) and small interfering RNAs (siRNAs); depletion of Dicer was found to impair the migration of endothelial cells. Methods: siRNA transfection, cell migration assay, real-time RT–PCR, chromatin immunoprecipitation, Western blotting, ELISA, caspase-3 activity assay, and annexin-V–FITC assay were utilized. Results: Knockdown of Dicer impairs the migratory capacity of HEK293T cells and induces fibronectin-1. The upregulation of fibronectin-1 is dependent on Egr1. Fibronectin-1/Dicer double-knockdown cells showed a marked increase in apoptosis compared with fibronectin-1 single knockdown cells. Conclusions: Decreased Dicer expression induces fibronectin-1 expression via an Egr1-dependent manner. General significance: Our data suggest that upregulation of fibronectin-1 protects Dicer knockdown HEK293T cells against apoptosis. [Copyright &y& Elsevier]