BACKGROUND: MicroRNAs are non-coding RNA molecules that posttranscriptionally 
regulate expression of target genes and have been implicated in the progress of 
cancer proliferation, differentiation and apoptosis. The aim of this study was 
to determine whether microRNA-21 (miR-21), a specific microRNA implicated in 
multiple aspects of carcinogenesis, impacts breast cancer invasion by regulating 
the tissue inhibitor of metalloproteinase 3 (TIMP3) gene.
METHODS: miR-21 expression was investigated in 32 matched breast cancer and 
normal breast tissues, and in four human breast cancer cell lines, by Taqman 
quantitative real-time PCR. Cell invasive ability was determined by matrigel 
invasion assay in vitro, in cells transfected with miR-21 or anti-miR-21 
oligonucleotides. In addition, the regulation of tissue inhibitor of 
metalloproteinase 3 (TIMP3) by miR-21 was evaluated by western blotting and 
luciferase assays.
RESULTS: Of the 32 paired samples analyzed, 25 breast cancer tissues displayed 
overexpression of miR-21 in comparison with matched normal breast epithelium. 
Additionally, incidence of lymph node metastasis closely correlated with miR-21 
expression, suggesting a role for miR-21 in metastasis. Similarly, each of the 
four breast cancer cell lines analyzed overexpressed miR-21, to varied levels. 
Further, cells transfected with miR-21 showed significantly increased matrigel 
invasion compared with control cells, whereas transfection with anti-miR-21 
significantly decreased cell invasion. Evaluation of TIMP3 protein levels, a 
peptidase involved in extarcellular matrix degredation, inversely correlated 
with miR-21 expression.
CONCLUSION: As knockdown of miR-21 increased TIMP3 protein expression and 
luciferase reporter activity, our data suggests that miR-21 could promote 
invasion in breast cancer cells via its regulation of TIMP3.