Affiliation:
1. Department of Oral Pathology, School of Dentistry and Dental Research Institute Seoul National University Seoul South Korea
2. Department of Dentistry Inje University Ilsan Paik Hospital Goyang South Korea
3. Department of Oral Pathology Seoul National University Dental Hospital Seoul South Korea
Abstract
AbstractObjectiveDownregulation of N‐myc downstream‐regulated gene 2 (NDRG2), a tumor suppressor gene, has been associated with poor clinical outcomes in various cancers. However, the prognostic significance of NDRG2 in oral squamous cell carcinoma (OSCC) remains unknown. This study aimed to evaluate the prognostic value of NDRG2 downregulation in OSCC and to elucidate the mechanism by which NDRG2 is downregulated and the biological role of NDRG2 in tumor progression.MethodsImmunohistochemical and in silico analyses of NDRG2 expression were performed, and the correlation between NDRG2 expression and clinicopathological data was analyzed. The effect of NDRG2 knockdown on the biological behavior of OSCC cells was investigated and the effect of 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) on NDRG2 expression was determined.ResultsNDRG2 expression was significantly downregulated and DNA hypermethylation of NDRG2 was frequently found in head and neck SCC, including OSCC. Low NDRG2 expression was significantly correlated with adverse clinicopathological features and worse survival in OSCC. NDRG2 knockdown could enhance the oncogenic properties of OSCC cells. NDRG2 mRNA levels in OSCC cells could be restored by 5‐aza‐dC.ConclusionDownregulation of NDRG2 promotes tumor progression and predicts poor prognosis in OSCC. Therefore, restoration of NDRG2 expression may be a potential therapeutic strategy in OSCC.
Funder
Ministry of Science and ICT, South Korea