MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and 
various types of hematological malignancies. To determine whether miR-21 
promotes tumor development in vivo, we knocked out the miR-21 allele in mice. In 
response to the 7,12-dimethylbenz[a]anthracene 
(DMBA)/12-O-tetradecanoylphorbol-13-acetate mouse skin carcinogenesis protocol, 
miR-21-null mice showed a significant reduction in papilloma formation compared 
with wild-type mice. We revealed that cellular apoptosis was elevated and cell 
proliferation was decreased in mice deficient of miR-21 compared to wild-type 
animals. In addition, we found that a large number of validated or predicted 
miR-21 target genes were up-regulated in miR-21-null keratinocytes, which are 
precursor cells to skin papillomas. Specifically, up-regulation of Spry1, Pten, 
and Pdcd4 when miR-21 was ablated coincided with reduced phosphorylation of ERK, 
AKT, and JNK, three major downstream effectors of Ras activation that plays a 
predominant role in DMBA-initiated skin carcinogenesis. These results provide in 
vivo evidence that miR-21 exerts its oncogenic function through negatively 
regulating its target genes.