Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression
Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression
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DOI：
10.3978/j.issn.1000-9604.2014.08.03
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发表时间：
2014-08-01
影响因子：
5.1
通讯作者：
Wu, Bin
中科院分区：
文献类型：
--
作者：
Li, Ming;Wang, Ying;Wu, Bin
目的：为了更好地了解DNA甲基转移酶1（DNMT 1）表达失调在肾透明细胞癌（ccRCC）的进展和生物学行为中的作用，我们采用免疫组化方法检测了89例ccRCC和22例正常组织中DNMT 1的表达差异。结果：DNMT 1基因在肾细胞癌中的表达明显高于非肿瘤组织（56.2%和27.3%），差异有统计学意义（P=0.018）; DNMT 1的表达与肿瘤大小、病理分期、组织学分级、淋巴结转移、血管浸润、复发及预后密切相关。结论：肾细胞癌组织中DNMT 1蛋白表达增高，DNMT 1表达与肾细胞癌患者预后不良有关。体外实验进一步表明DNMT 1在肾癌细胞的增殖和侵袭中起重要作用。此外，靶向这种酶可能是治疗ccRCC的有希望的策略，如通过抑制细胞活力、增加细胞凋亡、减少集落形成和侵袭能力所证明的。
Objective: To better understand the contribution of dysregulated DNA methyltransferase 1 (DNMT1) expression to the progression and biology of clear cell renal cell carcinoma (ccRCC).Methods: We examined the differences in the expression of DNMT1 in 89 ccRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability; apoptosis, colony formation and invading ability of ccRCC cell lines (786-0 and Caki-1) were assessed after transfection with DNMT1 siRNA.Results: We found DNMT1 protein was significantly higher expressed in ccRCC than that of in no-tumor tissues (56.2% and 27.3%, respectively, P=0.018). The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability.Conclusions: Expression of DNMT1 protein is increased in ccRCC tissues, and DNMT1 expression is associated with poor prognosis of patients. Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising strategy for treating ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability.