miR-34a Inhibits HNSCC Tumor Growth Figure 3. miR-34a significantly inhibits tumor cell migration. A: Tumor cell (UM-SCC-74A) motility was examined by scratch assay. Red dotted lines mark the edges at the start of experiments, and green dotted lines mark the edges at the end of experiments. B-C: Tumor cell migration was analyzed by Xcelligence system. Percentage cell migration for cells ectopically expressing miR-34 was calculated by adjusting migration index for tumor cells transduced with SC to 100%. *, represent a significant inhibition (p,0.05) of cell migration in miR-34a expressing tumor cells as compared to SC. doi:10.1371/journal.pone.0037601.g003 significantly inhibited the expression of the target proteins E2F3a/ b, SIRT1, survivin and CDK4 (Figure 7E). Discussion Head and neck squamous cell carcinomas (HNSCC) are the most frequent malignancies of the upper aerodigestive tract [41]. In many cases, these cancers are diagnosed at a very late stage (III or IV). These cancers are known to be very severe and they can strip away a person’s voice, distort the face and rob the basic abilities to eat, drink and swallow. Although advancements in the techniques for surgery, radiation and chemotherapy have in- creased the local control of HNSCC, the overall survival rates have not improved significantly over the last three decades [42,43]. The high mortality rate in these patients is in large measure due to local tissue invasion by the primary tumor as well as acquisition of resistance to chemotherapy and radiation PLoS ONE | www.plosone.org 5 May 2012 | Volume 7 | Issue 5 | e37601