Role of the RARRES1 gene in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a unique type of head and neck cancer that is most prevalent in southern China. Previous studies have suggested that genetic susceptibility, environmental carcinogens, and Epstein–Barr virus (EBV) infection contribute to the etiology of NPC. Our group has identified the retinoic acid receptor responder (tazarotene induced) 1 gene (RARRES1; alias TIG1) to be transcriptionally silenced by promoter hypermethylation in ∼90% of NPC cases, suggesting that its inactivation may be important in NPC formation. The aim of this study was to explore the functional role of the RARRES1 protein (alias TIG1) in NPC cells with EBV infection (HK1-EBV) and without (HK1). Cellular proliferation analysis, as measured by 5-bromo-2′-deoxyuridine (BrdU) incorporation, showed that knockdown and overexpression of TIG1 in HK1 led, respectively, to significantly increased (P = 0.005) and reduced (P = 0.027) proportions of BrdU-labeled cells, compared with control cells. In contrast, knockdown or overexpression of TIG1 had no significant effect on cellular proliferation in HK1-EBV cells. Invasion chamber assay showed that TIG1 knockdown in HK1-EBV cells resulted in significant enhancement of invasive capacity of HK1-EBV cells (P = 0.006). HK1 cells were not invasive, regardless of TIG1 status. These findings suggest that TIG1 may play a role in cellular proliferation and invasion in NPC cells and that its function may be dependent on the EBV status.