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. 2014 Aug;26(4):371-81.
doi: 10.3978/j.issn.1000-9604.2014.08.03.

Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression

Ming Li  1 , Ying Wang  1 , Yongsheng Song  1 , Renge Bu  1 , Bo Yin  1 , Xiang Fei  1 , Qizhen Guo  1 , Bin Wu  1
Affiliations

Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression

Ming Li et al. Chin J Cancer Res. 2014 Aug.

Abstract

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.

Keywords: Clear cell renal cell carcinoma (ccRCC); DNA methyltransferase 1 (DNMT1); immunohistochemistry; siRNA.

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Figures

Figure 1
Figure 1
Nuclear immunostaining of DNMT1 protein in no-tumor and ccRCC tissues (Original magnification: ×400). ccRCC, clear cell renal cell carcinoma; DNMT1, DNA methyltransferase 1.
Figure 2
Figure 2
Univariate analyses of OS and DSF in patients with ccRCC using the Kaplan-Meier method according to DNMT1 expression. The log rank test was used to calculate P values. OS, overall survival; DFS, disease-free survival; ccRCC, clear cell renal cell carcinoma; DNMT1, DNA methyltransferase 1.
Figure 3
Figure 3
Konckdown of DNMT1 expressions in ccRCC cells. DNMT1 siRNA was transiently transfected into ccRCC cell lines and then subjected to qRT-PCR (A) and western blotting (B) analysis for DNMT1 expression. a, P<0.05 compared with the untreated cells. b, P<0.05 compared with the negative siRNA cells. The dates are shown as the mean ± SD of six independent experiments. DNMT1, DNA methyltransferase 1; ccRCC, clear cell renal cell carcinoma.
Figure 4
Figure 4
Effects of DNMT1 siRNA on cell viability (A), apoptosis (B), colony formation (C) and invading ability of invation (D). a, P<0.05 compared with the untreated cells. b, P<0.05 compared with the negative siRNA transfected cells. The data are shown as the mean ± SD of eight independent experiments. DNMT1, DNA methyltransferase 1.
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