Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells

作者: L Y W Bourguignon , C Earle , G Wong , C C Spevak , K Krueger

DOI: 10.1038/ONC.2011.222

关键词:

摘要: MicroRNAs are often associated with the pathogenesis of many cancers, including head and neck squamous cell carcinoma (HNSCC). In particular, microRNA-21 (miR-21) appears to have a critical role in tumor survival, chemoresistance HNSCC progression. this study, we investigated matrix hyaluronan (HA)-induced CD44 (a primary HA receptor) interaction stem markers, Nanog Stat-3, cells (HSC-3 cells). Our results indicate that binding promotes Nanog-Stat-3 (also tyrosine phosphorylated Stat-3) complex formation, nuclear translocation transcriptional activation. Further analyses reveal miR-21 is controlled by an upstream promoter containing Stat-3 site(s), while chromatin immunoprecipitation assays demonstrate stimulation expression HA/CD44 signaling Nanog/Stat-3-dependent cells. This process decrease suppressor protein (PDCD4), upregulation i nhibitors apoptosis family proteins (IAPs) as well HSC-3 Treatment Nanog- and/or Stat-3-specific small interfering RNAs effectively blocks HA-mediated events, abrogates production increases PDCD4 expression. Subsequently, inhibition causes downregulation survival (IAP) enhancement chemosensitivity. To further evaluate cell-specific functions, were also transfected specific anti-miR-21 inhibitor order silence block its target functions. not only upregulates but decreases IAP enhances chemosensitivity HA-treated Together, these findings HA-induced has pivotal leading reduction, novel Nanog/Stat-3 pathway-specific mechanism involved significant for formation future intervention strategies treatment HA/CD44-activated HNSCC.

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