Promoter Methylation of Dual Specificity Phosphatase-6 Gene effect on Invasion and Metastasis of Nasopharyngeal Carcinoma

Yang Jh, S. Zhang
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Abstract

Objective: The dual-specificity phosphatase-6 (DUSP-6) is a member of dual-specificity protein phosphatase (DUSP) family, it can make residues of threonine and tyrosine dephosphorylate. In recent years, it was found that DUSP-6 is correlated with tumour generation and progress. In this study we have detected the effect of DUSP-6 gene methylation on invasion and metastasis of nasopharyngeal carcinoma. Methods: RT-PCR and methylation-specific PCR are used to detect mRNA expression and methylation state of DUSP-6 gene in nasopharyngeal carcinoma tissues and CNE2 cell line. The changes of mRNA expression and methylation state of DUSP-6 gene, proliferation and invasion of cells were detected after 5-aza- 2’-deoxycytidine (5-aza-cdR) treated CNE2 cell line. Results: These results showed that DUSP-6 gene expression is related to its promoter methylation state, cervical lymph node metastasis is related to DUSP-6 gene promoter methylation state in patients with nasopharyngeal carcinoma, 5-aza-cdR can inhibit invasion of CNE2 cells, and make re-expression of DUSP-6 gene by promoter demethylation in CNE2 cells. Conclusion: DUSP-6 gene promoter methylation state is possibly an important factor that effected invasion and metastasis of nasopharyngeal carcinoma. DUSP-6 gene may make a novel marker for prognostic evaluation in nasopharyngeal carcinoma.
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双特异性磷酸酶-6基因启动子甲基化对鼻咽癌侵袭转移的影响
目的:双特异性磷酸酶-6(DUSP-6)是双特异性蛋白磷酸酶(DUSP)家族的成员,它能使苏氨酸和酪氨酸残基去磷酸化。近年来,人们发现DUSP-6与肿瘤的发生和发展有关。本研究检测了DUSP-6基因甲基化对鼻咽癌侵袭转移的影响。方法:采用RT-PCR和甲基化特异性PCR方法检测DUSP-6基因在鼻咽癌组织和CNE2细胞系中的表达及甲基化状态。检测5-氮杂-2’-脱氧胞苷(5-aza-cdR)处理CNE2细胞后DUSP-6基因mRNA表达、甲基化状态、细胞增殖和侵袭的变化。结果:鼻咽癌患者DUSP-6基因表达与其启动子甲基化状态有关,颈淋巴结转移与DUSP-6启动子甲基状态有关,5-aza-cdR可抑制CNE2细胞的侵袭,并通过启动子去甲基化使DUSP-6在CNE2细胞中重新表达。结论:DUSP-6基因启动子甲基化状态可能是影响鼻咽癌侵袭转移的重要因素。DUSP-6基因可能成为鼻咽癌预后评估的新标志物。
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