miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα

MicroRNA-135a (miR-135a) down-modulates parameters of cancer progression and its expression is decreased in metastatic breast cancers (as compared to non-metastatic tumors) as well as in prostate tumors relative to normal tissue. These expression and activity patterns are opposite to those of the Estrogen-Related Receptor alpha (ERR alpha), an orphan member of the nuclear receptor family. Indeed high expression of ERR alpha correlates with poor prognosis in breast and prostate cancers, and the receptor promotes various traits of cancer aggressiveness including cell invasion. Here we show that miR-135a down-regulates the expression of ERR alpha through specific sequences of its 3'UTR. As a consequence miR-135a also reduces the expression of downstream targets of ERR alpha. miR-135a also decreases cell invasive potential in an ERR alpha-dependent manner. Our results suggest that the decreased expression of miR-135a in metastatic tumors leads to elevated ERR alpha expression, resulting in increased cell invasion capacities.