To determine the mechanism of action of miR-221 and miR-222 in glioma cell invasion, we performed a miRNA target search using TargetScan and found that the “seed sequence” of miR-221 and miR-222 matched the 3′ UTR of the TIMP3 gene (Figure 3A), which has been evidenced in non small cell lung cancer cells.[12] To detect whether TIMP3 is indeed regulated by miR-221 and miR-222 in glioma cells, we knocked-down miR-221/222 and ectopically expressed miR-221/222 in U251 and LN229 cells. Here, TIMP3 is linked to glioma.