关键词: N‐myc downstream‐regulated gene 2 oral squamous cell carcinoma prognosis tumor progression tumor suppressor gene

来  源:   DOI:10.1111/odi.15045

Abstract:
OBJECTIVE: Downregulation 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.
METHODS: Immunohistochemical 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.
RESULTS: NDRG2 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.
CONCLUSIONS: Downregulation of NDRG2 promotes tumor progression and predicts poor prognosis in OSCC. Therefore, restoration of NDRG2 expression may be a potential therapeutic strategy in OSCC.
摘要:
目的:下调N-myc下游调节基因2(NDRG2),肿瘤抑制基因,与各种癌症的不良临床结果有关。然而,NDRG2在口腔鳞状细胞癌(OSCC)中的预后意义尚不清楚.本研究旨在评估OSCC中NDRG2下调的预后价值,并阐明NDRG2下调的机制以及NDRG2在肿瘤进展中的生物学作用。
方法:进行NDRG2表达的免疫组织化学和计算机模拟分析,分析NDRG2表达与临床病理资料的相关性。研究了NDRG2敲低对OSCC细胞生物学行为的影响,并确定了5-氮杂-2'-脱氧胞苷(5-氮杂-dC)对NDRG2表达的影响。
结果:NDRG2表达显著下调,NDRG2的DNA甲基化在头颈部SCC中常见,包括OSCC。低NDRG2表达与OSCC不良临床病理特征和较差生存率显著相关。NDRG2敲低可以增强OSCC细胞的致癌特性。5-aza-dC可以恢复OSCC细胞中NDRG2的mRNA水平。
结论:在OSCC中,NDRG2的下调促进肿瘤进展并预测预后不良。因此,NDRG2表达的恢复可能是OSCC潜在的治疗策略。
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