The present results provide evidence that MELK serves a key role in CSCs through the regulation of SOX2 and further indicates that MELK inhibition may also be promising for clinical applications in the treatment of HNSCC.
As a result, VPA inhibited the self-renewal abilities of HNSCC CSCs during two serial passages and decreased the expression of stem cell markers, such as Oct4, Sox2 and CD44.
Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR.
Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs.