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Background: This study was performed to investigate the effect of microRNA-203 (miR-203) and ΔNp63 on cell proliferation and the functional connection between miR-203 and ΔNp63 in ESCC. Methods: We employed 2 human ESCC cell lines, Eca109 and TE-1, as the model system. The effect of miR-203 and ΔNp63 on cell proliferation was determined in cells transfected with miR-203 mimic and ΔNp63 small interfering RNA (siRNA), respectively. The regulation of ΔNp63 expression in ESCC cells by miR-203 was studied by luciferase reporter assay, RT-PCR and western blot analysis in cells transfected with miR-203. The effect of ΔNp63 reexpression on miR-203 induced inhibition of cell proliferation was studied by cell proliferation assay in cells cotransfected with miR-203 and pcDNA-ΔNp63 plasmid (without the 3'-UTR of ?Np63). Results: We found that both miR-203 and ΔNp63 siRNA signicantly inhibited cell proliferation in ESCC. MiR-203 could down-regulate endogenous ΔNp63 expression at the posttranscriptional level. Moreover, re-expression of ΔNp63 in cells transfected with miR-203 significantly attenuated the miR-203 induced inhibition of cell proliferation. Conclusions: Our data implied that miR-203 could inhibit cell proliferation in human ESCC through ΔNp63-mediated signal pathway. Therefore, we propose that miR-203 might be used as a therapeutic agent for human ESCC. [ABSTRACT FROM AUTHOR]