The activities of RNA-binding proteins are perturbed in several pathological 
conditions, including cancer. These proteins include tristetraprolin (TTP, 
ZFP36) and HuR (ELAVL1), which respectively promote the decay or stability of 
adenylate-uridylate-rich (AU-rich) mRNAs. Here, we demonstrated that increased 
stabilization and subsequent over-expression of HuR mRNA were coupled to TTP 
deficiency. These findings were observed in breast cancer cell lines with an 
invasive phenotype and were further confirmed in ZFP36-knockout mouse 
fibroblasts. We show that TTP-HuR imbalance correlated with increased expression 
of AU-rich element (ARE) mRNAs that code for cancer invasion genes. The microRNA 
miR-29a was abundant in invasive breast cancer cells when compared to 
non-tumourigenic cell types. When normal breast cells were treated with miR-29a, 
HuR mRNA and protein expression were up-regulated. MiR-29a recognized a seed 
target in the TTP 3' UTR and a cell-permeable miR-29a inhibitor increased TTP 
activity towards HuR 3' UTR. This led to HuR mRNA destabilization and 
restoration of the aberrant TTP-HuR axis. Subsequently, the cancer invasion 
factors uPA, MMP-1 and MMP-13, and cell invasiveness, were decreased. The 
TTP:HuR mRNA ratios were also perturbed in samples from invasive breast cancer 
patients when compared with normal tissues, and were associated with invasion 
gene expression. This study demonstrates that an aberrant ARE-mediated pathway 
in invasive cancer can be normalized by targeting the aberrant and functionally 
coupled TTP-HuR axis, indicating a potential therapeutic approach.