It was found that the Hyaluronan/CD44 interaction with the novel Nanog and Stat-3 signaling pathway plays a crucial role in miRNA-21 production, which leads to a decline in tumor suppressor protein (PDCD4), an increase in inhibitors of the apoptosis family of proteins (IAPs) and chemoresistance in Hyaluronan-treated HNSCC cells (14). This evidence concerns the gene STAT3 and head and neck squamous cell carcinoma.