Evaluation of tryptophan-aspartic acid repeat-containing protein 34 as a novel tumor-suppressor molecule in human oral cancer

Highlights: • WDR34 contributes to tumor growth in OSCCs. • WDR34 regulates the cell-cycle arrest at G1 phase in OSCC cells. • WDR34 controls NF-κB activity though specific inhibition of TAK1 activity. • WDR34 is critical molecule for control of tumor progression by regulating IL-6 expression. • WDR34 might be a potential tumor suppressor molecule in OSCCs. Tryptophan-aspartic acid (WD) repeat-containing protein 34 (WDR34), one of the WDR protein superfamilies with five WD40 domains, inhibits a transforming growth factor-beta (TGF-β) activated kinase 1 (TAK1)-associated NF-κB activation pathway. Nevertheless, little is known about the roles of WDR34 in cancer. The current study sought to elucidate the clinical relevance of WDRsfb34 in oral squamous cell carcinoma (OSCC). We found WDR34 down-regulation in OSCCs compared with normal control tissues using real-time quantitative reverse transcription-polymerase chain reaction, immunoblotting, and immunohistochemistry. Models of overexpression of WDR34 (oeWDR34) showed depressed cellular growth through cell-cycle arrest at the G1 phase. To investigate the inhibitory function of WDR34, we challenged oeWDR34 cells with interleukin (IL)-1, a ligand for activation of the TAK1-NF-κB pathway and assessed the expression of a target gene of the pathway. oeWDR34 strongly inhibited IL-6 expression, which is closely related to tumoral growth, compared with control cells, suggesting that WDR34 would be a critical molecule for control of tumoral progression. In addition to the in vitro experiments, WDR34 negativity was correlated with tumoral growth of OSCCs. Our findings suggested that WDR34 inhibits OSCC progression and might be a potential tumor-suppressor molecule in OSCCs.