Despite tremendous efforts worldwide from clinicians and cancer scientists, 
pancreatic ductal adenocarcinoma (PDA) remains a deadly disease for which no 
cure is available. Recently, microRNAs (miRNAs) have emerged as key actors in 
carcinogenesis and we demonstrated that microRNA-21 (miR-21), oncomiR is 
expressed early during PDA. In the present study, we asked whether targeting 
miR-21 in human PDA-derived cell lines using lentiviral vectors (LVs) may impede 
tumor growth. We demonstrated that LVs-transduced human PDA efficiently 
downregulated miR-21 expression, both in vitro and in vivo. Consequently, cell 
proliferation was strongly inhibited and PDA-derived cell lines died by 
apoptosis through the mitochondrial pathway. In vivo, miR-21 depletion stopped 
the progression of a very aggressive model of PDA, to induce cell death by 
apoptosis; furthermore, combining miR-21 targeting and chemotherapeutic 
treatment provoked tumor regression. We demonstrate herein for the first time 
that targeting oncogenic miRNA strongly inhibit pancreatic cancer tumor growth 
both in vitro and in vivo. Because miR-21 is overexpressed in most human tumors; 
therapeutic delivery of miR-21 antagonists may still be beneficial for a large 
number of cancers for which no cure is available.