Subgroup analysis indicted that high expression of CD133 (HR = 2.33, 95%CI: 1.42-3.83, P < 0.001), Oct-4(HR = 2.10, 95%CI: 1.36-3.22, P = 0.007) and Nanog (HR = 2.49, 95%CI: 1.66-3.72, P < 0.001) could predict poor OS in HNSCC patients respectively whereas overexpression of Bmi-1 was not related to the reduced OS in HNSCC patients (HR = 1.32, 95%CI: 0.66-2.65, P = 0.43).
Constitutive activation of NICD promoted the self-renewal capacity of HNSCC cells by activating sphere formation and increased the expression of stem cell markers such as Oct4, Sox2, and CD44.
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.
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.