Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Aberrant Methylation of the 1p36 Tumor Suppressor Gene RIZ1 in Renal Cell Carcinoma

  • Ge, Peng (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University) ;
  • Yu, Xi (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University) ;
  • Wang, Zi-Cheng (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University) ;
  • Lin, Jian (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University)
  • Published : 2015.05.18
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Abstract

Background: Retinoblastoma protein-interacting zinc finger gene 1(RIZ1) functions as a tumor suppressor. Hypermethylation-mediated RIZ1 silencing has been reported in several cancers, but not in renal cell carcinoma (RCC) yet. Materials and Methods: We examined the RIZ1 expression and methylation in a panel of RCC cell lines and 50 primary tumors using semiquantitative/quantitative polymerase chain reaction (PCR), methylation specific PCR, and bisulfite sequencing genomic. We also explored the relationship between methylation status of RIZ1 and clinicopathological features in RCC patients. Results: RIZ1 expression was down-regulated or lost in OS-RC-2, 769-P, Caki-1, 786-O and A498 RCC cell lines. Restored expression of RIZ1 was detected after addition of 5-aza-2'-deoxycytidine with/without trichostatin A, suggesting that DNA methylation directly mediates its silencing. The RIZ1 expression was significantly reduced in RCCs compared to adjacent non-malignant renal samples (P<0.001). Aberrant methylation was detected in 15 of 50 (30%) RCCs and in 2 of 28 (7%) adjacent non-malignant renal samples (P=0.02). No statistically significant correlation between methylated and unmethylated cases with regard to age, gender, pathological stage and grade was observed. Conclusions: RIZ1 expression is down-regulated in human RCC, and this down-regulation is associated with methylation. RIZ1 methylation may play a role in renal carcinogenesis.

Keywords

References

  1. Buyse IM, Shao G, Huang S (1995). The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein. Proc Natl Acad Sci U S A, 92, 4467-71. https://doi.org/10.1073/pnas.92.10.4467
  2. Cheng HY, Gao Y, Lou G (2010). DNA methylation of the RIZ1 tumor suppressor gene plays an important role in the tumorigenesis of cervical cancer. Eur J Med Res, 15, 20-4. https://doi.org/10.1186/2047-783X-15-1-20
  3. de Martino M, Klatte T, Haitel A, Marberger M (2012). Serum cell-free DNA in renal cell carcinoma: a diagnostic and prognostic marker. Cancer, 118, 82-90. https://doi.org/10.1002/cncr.26254
  4. Dong SW, Zhang P, Liu YM, et al (2012). Study on RIZ1 gene promoter methylation status in human esophageal squamous cell carcinoma. World J Gastroenterol, 18, 576-82. https://doi.org/10.3748/wjg.v18.i6.576
  5. Du Y, Carling T, Fang W, et al (2001). Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily. Cancer Res, 61, 8094-9.
  6. Eble JN, Epstein JI, Sesterhenn IA (2004). Pathology and genetics of tumors of the urinary system and male genital organs. IARC Press, Lyon.
  7. Ellinger J, Holl D, Nuhn P, et al (2011). DNA hypermethylation in papillary renal cell carcinoma. BJU Int, 107, 664-9. https://doi.org/10.1111/j.1464-410X.2010.09468.x
  8. Esteller M (2007). Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet, 8, 286-98. https://doi.org/10.1038/nrg2005
  9. Garcia-Baquero R, Puerta P, Beltran M, et al (2013). Methylation of a novel panel of tumor suppressor genes in urine moves forward noninvasive diagnosis and prognosis of bladder cancer: a 2-center prospective study. J Urol, 190, 723-30. https://doi.org/10.1016/j.juro.2013.01.105
  10. Gnyszka A, Jastrzebski Z, Flis S (2013). DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer. Anticancer Res, 33, 2989-96.
  11. Greene FL, Page DL, Fleming ID, et al (2002). AJCC cancer staging manual, 6th edn. Springer publisher, New York.
  12. Haroun RA, Zakhary NI, Mohamed MR, et al (2014). Assessment of the prognostic value of methylation status and expression levels of FHIT, GSTP1 and p16 in non-small cell lung cancer in Egyptian patients. Asian Pac J Cancer Prev, 15, 4281-7. https://doi.org/10.7314/APJCP.2014.15.10.4281
  13. Hasegawa Y, Matsubara A, Teishima J, et al (2007). DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer. Cancer Sci, 98, 32-6. https://doi.org/10.1111/j.1349-7006.2006.00338.x
  14. Hauser S, Zahalka T, Fechner G, et al (2013). Serum DNA hypermethylation in patients with kidney cancer: results of a prospective study. Anticancer Res, 33, 4651-6.
  15. He L, Yu JX, Liu L, et al (1998). RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis. Cancer Res, 58, 4238-44.
  16. Hoffman AM, Cairns P (2011). Epigenetics of kidney cancer and bladder cancer. Epigenomics, 3, 19-34. https://doi.org/10.2217/epi.10.64
  17. Huang S, Shao G, Liu L (1998). The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J Biol Chem, 273, 15933-9. https://doi.org/10.1074/jbc.273.26.15933
  18. Khaenam P, Jearanaikoon P, Pairojkul C, et al (2010). Genetic and epigenetic alterations of RIZ1 and the correlation to clinicopathological parameters in liver fluke-related cholangiocarcinoma. Exp Ther Med, 1, 385-390.
  19. Knudson AG (2001). Two genetic hits (more or less) to cancer. Nat Rev Cancer, 1, 157-62. https://doi.org/10.1038/35101031
  20. Lal G, Padmanabha L, Smith BJ, et al (2006). RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma. Cancer, 107, 2752-9. https://doi.org/10.1002/cncr.22325
  21. Miyamoto K, Ushijima T (2005). Diagnostic and therapeutic applications of epigenetics. Jpn J Clin Oncol, 35, 293-301. https://doi.org/10.1093/jjco/hyi088
  22. Pastural E, Takahashi N, Dong WF, et al (2007). RIZ1 repression is associated with insulin-like growth factor-1 signaling activation in chronic myeloid leukemia cell lines. Oncogene, 26, 1586-94. https://doi.org/10.1038/sj.onc.1209959
  23. Raja UM, Gopal G, Rajkumar T (2012). Intragenic DNA methylation concomitant with repression of ATP4B and ATP4A gene expression in gastric cancer is a potential serum biomarker. Asian Pac J Cancer Prev, 13, 5563-8. https://doi.org/10.7314/APJCP.2012.13.11.5563
  24. Sasaki O, Meguro K, Tohmiya Y, et al (2002). Altered expression of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukaemia. Br J Haematol, 119, 940-8. https://doi.org/10.1046/j.1365-2141.2002.03972.x
  25. Steele-Perkins G, Fang W, Yang XH, et al (2001). Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein-methyltransferase superfamily. Genes Dev, 15, 2250-62. https://doi.org/10.1101/gad.870101
  26. Sun W, Qiao L, Liu Q, et al (2011). Anticancer activity of the PR domain of tumor suppressor RIZ1. Int J Med Sci, 8, 161-7.
  27. Tokumaru Y, Nomoto S, Jeronimo C, et al (2003). Biallelic inactivation of the RIZ1 gene in human gastric cancer. Oncogene, 22, 6954-8. https://doi.org/10.1038/sj.onc.1206403
  28. Xie M, Shao G, Buyse IM, Huang S (1997). Transcriptional repression mediated by the PR domain zinc finger gene RIZ. J Biol Chem, 272, 26360-6. https://doi.org/10.1074/jbc.272.42.26360
  29. Zhang Q, Ying J, Li J, et al (2010). Aberrant promoter methylation of DLEC1, a critical 3p22 tumor suppressor for renal cell carcinoma, is associated with more advanced tumor stage. J Urol, 184, 731-7. https://doi.org/10.1016/j.juro.2010.03.108
  30. Zhang Q, Ying J, Zhang K, et al (2007). Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell carcinoma. Cancer Lett, 249, 220-6. https://doi.org/10.1016/j.canlet.2006.08.019
  31. Zhang Q, Zhang L, Li L, et al (2014). Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis. Cancer Lett, 354, 227-34. https://doi.org/10.1016/j.canlet.2014.07.040

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