Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Effects of Down-regulation of HDAC6 Expression on Proliferation, Cell Cycling and Migration of Esophageal Squamous Cell Carcinoma Cells and Related Molecular Mechanisms

  • Li, Ning (The Cancer Diagnosis-Treatment Center of The First People's Hospital of Kaifeng) ;
  • Tie, Xiao-Jing (The Cancer Diagnosis-Treatment Center of The First People's Hospital of Kaifeng) ;
  • Liu, Pei-Jie (The Cancer Diagnosis-Treatment Center of The First People's Hospital of Kaifeng) ;
  • Zhang, Yan (The Cancer Diagnosis-Treatment Center of The First People's Hospital of Kaifeng) ;
  • Ren, Hong-Zheng (The Cancer Diagnosis-Treatment Center of The First People's Hospital of Kaifeng) ;
  • Gao, Xin (The Cancer Diagnosis-Treatment Center of The First People's Hospital of Kaifeng) ;
  • Xu, Zhi-Qiao (The Cancer Diagnosis-Treatment Center of The First People's Hospital of Kaifeng)
  • Published : 2013.02.28
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Abstract

Objective: To study the effects of down-regulation of HDAC6 expression on proliferation, cell cycling and migration of esophageal squamous cell carcinoma (ESCC) cells and related molecular mechanisms. Methods: ESCC cell line EC9706 cells were randomly divided into untreated (with no transfection), control siRNA (transfected with control siRNA) and HDAC6 siRNA (transfected with HDAC6 small interfering RNA) groups. Effects of HDAC6 siRNA interference on expression of HDAC6 mRNA and protein in EC9706 cells were investigated by semi-quantitative RT-PCR, Western blotting and immunocytochemistry methods. Effects of down-regulation of HDAC6 expression on cell proliferation, cell cycle, and cell migration were studied using a CCK-8 kit, flow cytometry and Boyden chambers, respectively. Changes of mRNA and protein expression levels of cell cycle related factor (p21) and cell migration related factor (E-cadherin) were investigated by semi-quantitative RT-PCR and Western blotting methods. Results: After transfection of HDAC6 siRNA, the expression of HDAC6 mRNA and protein in EC9706 cells was significantly downregulated. In the HDAC6 siRNA group, cell proliferation was markedly inhibited, the percentage of cells in G0/G1 phase evidently increased and the percentage of cells in S phase decreased, and the number of migrating cells significantly and obviously decreased. The mRNA and protein expression levels of p21 and E-cadherin in the HDAC6 siRNA group were significantly higher than those in the untreated group and the control siRNA group, respectively. Conclusions: HDAC6 siRNA can effectively downregulate the expression of HDAC6 mRNA and protein in EC9706 cells. Down-regulation of HDAC6 expression can obviously inhibit cell proliferation, arrest cell cycling in the G0/G1 phase and reduce cell migration. The latter two functions may be closely related with the elevation of mRNA and protein expression of p21 and E-cadherin.

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References

  1. Ai J, Wang Y, Dar JA, et al (2009). HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer. Mol Endocrinol, 23, 1963-72. https://doi.org/10.1210/me.2009-0188
  2. Baker M (2010). RNA interference: Homing in on delivery. Nature, 464, 1225-8.
  3. Banerjee HN, Verma M (2009). Epigenetic mechanisms in cancer. Biomark Med, 3, 397-410. https://doi.org/10.2217/bmm.09.26
  4. Barnes PJ, Adcock IM (2009). Glucocorticoid resistance in inflammatory diseases. Ancet, 373, l905-l7.
  5. Carew JS, Giles FJ, Nawrocki ST (2008). Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett, 269, 7-17. https://doi.org/10.1016/j.canlet.2008.03.037
  6. Carter CL, Lin C, Liu CY, et al (2010). Phosphorylated p68 RNA helicase activates Snail1 transcription by promoting HDAC1 dissociation from the Snail1 promoter. Oncogene, 29, 5427-36. https://doi.org/10.1038/onc.2010.276
  7. Chen J, Zhou H, Li Q, et al (2011). Epigenetic modification of RhoE expression in gastric cancer cells. Oncol Rep, 25, 173-80.
  8. Duong V, Bret C, Altucci L, et al (2008). Specific activity of class II histone deacetylases in human breast cancer cells. Mol Cancer Res, 6, 1908-19. https://doi.org/10.1158/1541-7786.MCR-08-0299
  9. Fan LH, Li LX, Wei YC (2006). The Value of Immunocytochemistry in the Cytological Diagnosis of Serous Ef fusion. J Mod Lb Med, 21, 6-8.
  10. He QX, Zhu QJ, Chen JO, et al (2006). Application of immunocytochemistry to cytological diagnosis in hydrothorax and ascites. J Wenzhou Med College, 36, 466-8.
  11. Hideshima T, Bradner JE, Wong J, et al (2005). Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci USA, 102, 8567-72. https://doi.org/10.1073/pnas.0503221102
  12. Hrzenjak A, Moinfar F, Kremser ML, et al (2005). Valproate inhibition of histone deacetylase 2 affects differentiation and decreases proliferation of endometrial stromal sarcoma cells. Mol Cancer Ther, 5, 2203-10.
  13. Husain M, Harrod KS (2009). Influenza A virus-induced caspase-3 cleaves the histone deacetylase 6 in infected epithelial cells. FEBS Lett, 583, 2517-20. https://doi.org/10.1016/j.febslet.2009.07.005
  14. Jiang XX, Zhang QL,Wu WL, et al (2009). Synergistic effects of proteasome inhibitor and Histone Deacetylase Inhibitor on apoptosis and aggresome formation in T Lymphoma cells. J Experim Hematol, 17, 1232-6.
  15. Kakihana M, Ohira T, Chan D, et al (2009). Induction of E-cadherin in lung cancer and interaction with growth suppression by histone deacetylase inhibition. J Thorac Oncol, 4, 1455-65. https://doi.org/10.1097/JTO.0b013e3181bc9419
  16. Kawaguchi Y, Kovacs JJ, McLaurin A, et al (2003). The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell, 115, 727-38. https://doi.org/10.1016/S0092-8674(03)00939-5
  17. Kuwano H, Watanabe M, Sadanaga N, et al (1993). Squamous epithelial dysplasia associated with squamous cell carcinoma of the esophagus. Cancer Lett, 72, 141-7. https://doi.org/10.1016/0304-3835(93)90120-X
  18. Parkin DM (2000). Global cancer statistics in the year 2000. Lancet Oncol, 2, 533-43.
  19. Parkin DM, Bray FI, Devesa SS (2001). Cancer burden in the year 2000. The global picture. Eur J Cancer, 8, S4-66.
  20. Rey M, Irondelle M, Waharte F, et al (2010). HDAC6 is required for invadopodia activity and invasion by breast tumor cells. Eur J Cell Biol, 12, 25-30.
  21. Sakuma T, Uzawa K, Onda T, et al (2006). Aberrant expression of histone deacetylase 6 in oral squamous cell carcinoma. Int J Oncol, 29, 117-24.
  22. Shen J, Wang WQ (2011). Enhancement of sensitivity of oral squamous carcinoma cells to cytochrome c mediated apoptosis by histone deacetylase inhibitors. J Med Res, 40, 62-6.
  23. Shen R, Chinnaiyan AM, Ghosh D (2008). Pathway analysis reveals function al convergence of gene expression profiles in breast cancer. BMC Med Genomics, 1, 28. https://doi.org/10.1186/1755-8794-1-28
  24. Unoki M (2011). Current and Potential Anticancer Drugs Targeting Members of the UHRF1 Complex Including Epigenetic Modifiers. Recent Pat Anticancer Drug Discov, 6, 116-30. https://doi.org/10.2174/157489211793980024
  25. Westendorf JJ, Zaidi SK, Cascino JE, et al (2002). Runx2 (Cbfa1, AML-3) interacts with histone deacetylase 6 and represses the p21(CIP1/WAF1) promoter. Mol Cell Biol, 22, 7982-92. https://doi.org/10.1128/MCB.22.22.7982-7992.2002
  26. Wilson AJ, Byun DS, Popova N, et al (2006). Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem, 281, 13548-58. https://doi.org/10.1074/jbc.M510023200
  27. Wu Y, Song SW, Sun J, et al (2010). IIp45 inhibits cell migration through inhibition of HDAC6. J Biol Chem, 285, 3554-60. https://doi.org/10.1074/jbc.M109.063354
  28. Xu C, Lee SA, Chen X (2011). RNA interference as therapeutics for hepatocellular carcinoma. Recent Pat Anticancer Drug Discov, 6, 105-15.
  29. Yuan Q, Ye YJ, Fan YS (2006). The application of immunocytochemistrymarkers in cytological differential diagnosis of effusi on smear. 1, 50-3.
  30. Zhang H, Chen SH, Li YM (2004). Epidemiological investigation of esophageal carcinoma. World J Gastroenterol, 10, 1834-5.
  31. Zhang J, He Y, Wand SK, et al (2012). Expression of E-cadherin in the tumor tissue and serum of patients with esophageal squamous cell carcinoma. J Central South Univ (Medical Science), 3, 228-32.
  32. Zhang XG, Li Z, Wang JF, et al (2009). Evaluation of risk factors and prevention strategies of esophageal cancer. World Chinese J Digestol, 17, 677-80.
  33. Zhang ZH, Zhao LL, Guo HQ, et al (2008). Application of thin-layer cytology smears and immunocytochemistry in identifying the cell types of malignant tumors. JOURNAL??? 35, 332-5.

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