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Article

5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene

  • Authors:
    • Xiaorong Wang
    • E. Chen
    • Xue Yang
    • Yin Wang
    • Zhen Quan
    • Xiaohou Wu
    • Chunli Luo
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, P.R. China, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
  • Pages: 1375-1384
    |
    Published online on: December 17, 2015
       https://doi.org/10.3892/or.2015.4492
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Abstract

Hepatocyte cell adhesion molecule (hepaCAM), a tumor-suppressor gene, is rarely expressed in bladder carcinoma. However, little is known concerning the mechanisms of low hepaCAM expression in bladder cancer. Abnormal hypermethylation in the promoter plays a crucial role in cancer by silencing tumor-suppressor genes, which is catalyzed by DNA methyltransferases (DNMTs). In the present study, a total of 31 bladder cancer and 22 adjacent tissues were assessed by immunohistochemistry to detect DNMT3A/3B and hepaCAM expression. Methylation of hepaCAM was determined by methylation‑specific polymerase chain reaction (MSP). The mRNA and protein levels of DNMT3A/3B and hepaCAM were determined by RT-PCR and western blot analysis after treatment with 5-azacytidine (AZAC). Following AZAC treatment, the proliferation of bladder cancer cells was detected by CCK-8 and colony formation assays. Cell cycle distribution was examined by flow cytometry. To further evaluate the tumor‑suppressive roles of AZAC and the involved mechanisms, the anti-tumorigenicity of AZAC was tested in vivo. The expression of DNMT3A/3B protein was markedly increased in the bladder carcinoma tissues (P<0.05), and had a negative linear correlation with hepaCAM expression in the same patients according to Pearson's analysis (r=-0.7176/-0.7127, P<0.05). The MSP results indicated that the hepaCAM gene was hypermethylated in three bladder cancer cell lines. Furthermore, we found that downregulation of DNMT3A/3B expression, after treatment with AZAC, reversed the hypermethylation and expression of hepaCAM in bladder cancer cells. In addition, AZAC inhibited the proliferation of bladder cancer cells and arrested cells at the G0/G1 phase. The in vivo results showed that expression of DNMT3A/3B and hepaCAM as well as tumor growth of nude mice were markedly altered which corresponded with the in vitro results. Due to the ability to reactivate expression of hepaCAM and inhibit growth of bladder cancer cells, AZAC may represent an effective treatment for bladder cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Chen E, Yang X, Wang Y, Quan Z, Wu X and Luo C: 5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene. Oncol Rep 35: 1375-1384, 2016.
APA
Wang, X., Chen, E., Yang, X., Wang, Y., Quan, Z., Wu, X., & Luo, C. (2016). 5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene. Oncology Reports, 35, 1375-1384. https://doi.org/10.3892/or.2015.4492
MLA
Wang, X., Chen, E., Yang, X., Wang, Y., Quan, Z., Wu, X., Luo, C."5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene". Oncology Reports 35.3 (2016): 1375-1384.
Chicago
Wang, X., Chen, E., Yang, X., Wang, Y., Quan, Z., Wu, X., Luo, C."5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene". Oncology Reports 35, no. 3 (2016): 1375-1384. https://doi.org/10.3892/or.2015.4492
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Chen E, Yang X, Wang Y, Quan Z, Wu X and Luo C: 5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene. Oncol Rep 35: 1375-1384, 2016.
APA
Wang, X., Chen, E., Yang, X., Wang, Y., Quan, Z., Wu, X., & Luo, C. (2016). 5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene. Oncology Reports, 35, 1375-1384. https://doi.org/10.3892/or.2015.4492
MLA
Wang, X., Chen, E., Yang, X., Wang, Y., Quan, Z., Wu, X., Luo, C."5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene". Oncology Reports 35.3 (2016): 1375-1384.
Chicago
Wang, X., Chen, E., Yang, X., Wang, Y., Quan, Z., Wu, X., Luo, C."5-Azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene". Oncology Reports 35, no. 3 (2016): 1375-1384. https://doi.org/10.3892/or.2015.4492
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