DOI QR코드

DOI QR Code

Promoter Methylation Status of Two Novel Human Genes, UBE2Q1 and UBE2Q2, in Colorectal Cancer: a New Finding in Iranian Patients

  • Mokarram, Pooneh (Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences) ;
  • Shakiba-Jam, Fatemeh (Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences) ;
  • Kavousipour, Soudabeh (School of Advanced Medical Science and Technologies, Shiraz University of Medical Sciences) ;
  • Sarabi, Mostafa Moradi (Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences) ;
  • Seghatoleslam, Atefeh (Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences)
  • Published : 2016.01.11

Abstract

Background: The ubiquitin-proteasome system (UPS) degrades a variety of proteins which attach to specific signals. The ubiquitination pathway facilitates degradation of damaged proteins and regulates growth and stress responses. This pathway is altered in various cancers, including acute lymphoblastic leukemia, head and neck squamous cell carcinoma and breast cancer. Recently it has been reported that expression of newly characterized human genes, UBE2Q1 and UBE2Q2, putative members of ubiquitin-conjugating enzyme family (E2), has been also changed in colorectal cancer. Epigenetics is one of the fastest-growing areas of science and nowadays has become a central issue in biological studies of diseases. According to the lack of information about the role of epigenetic changes on gene expression profiling of UBE2Q1 and UBE2Q2, and the presence of CpG islands in the promoter of these two human genes, we decided to evaluate the promoter methylation status of these genes as a first step. Materials and Methods: The promoter methylation status of UBE2Q1 and UBE2Q2 was studied by methylation-specific PCR (MSP) in tumor samples of 60 colorectal cancer patients compared to adjacent normal tissues and 20 non-malignant controls. The frequency of the methylation for each gene was analyzed by chi-square method. Results: MSP results revealed that UBE2Q2 gene promoter were more unmethylated, while a higher level of methylated allele was observed for UBE2Q1 in tumor tissues compared to the adjacent normal tissues and the non malignant controls. Conclusions: UBE2Q1 and UBE2Q2 genes show different methylation profiles in CRC cases.

Keywords

UBE2Q1;UBE2Q2;promoter methylation;colorectal cancer

Acknowledgement

Supported by : Shiraz University of Medical sciences

References

  1. Arvand A, Bastians H, Welford SM, et al (1998). EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction. Oncogene, 17, 2039-45. https://doi.org/10.1038/sj.onc.1202129
  2. Asiaf A, Ahmad St, Fau - Aziz SA, et al (2014). Loss of expression and aberrant methylation of the CDH1 (E-cadherin) gene in breast cancer patients from Kashmir. Asian Pac J Cancer Prev, 15, 6397-403. https://doi.org/10.7314/APJCP.2014.15.15.6397
  3. Atefeh Seghatoleslam AZ (2009). Effects of over-expression of loc92912 gene on cell cycle progression. IJMS, 34, 277-84.
  4. Banerjee S, Brooks Ws Fau - Crawford DF, Crawford DF (2007). Inactivation of the ubiquitin conjugating enzyme UBE2Q2 causes a prophase arrest and enhanced apoptosis in response to microtubule inhibiting agents. Oncogene, 4, 6509-17.
  5. Bassermann F, Pagano M (2010). Dissecting the role of ubiquitylation in the DNA damage response checkpoint in G2. Cell Death Differ, 17, 78-85. https://doi.org/10.1038/cdd.2009.104
  6. Bremm A, Komander D (2011). Emerging roles for Lys11-linked polyubiquitin in cellular regulation. Trends Biochem Sci, 36, 355-63.
  7. Burger AM, Seth AK (2004). The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications. Eur J Cancer, 40, 2217-29. https://doi.org/10.1016/j.ejca.2004.07.006
  8. Chang R, Wei L, Lu Y, et al (2014). Upregulated expression of ubiquitin-conjugating enzyme E2Q1 (UBE2Q1) is associated with enhanced cell proliferation and poor prognosis in human hapatocellular carcinoma. J Mol Histol, 46, 45-56.
  9. Chen A, Kleiman FE, Manley JL, et al (2002). Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase. J Biol Chem, 277, 22085-92. https://doi.org/10.1074/jbc.M201252200
  10. Chen L, Madura K (2005). Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer Res, 65, 5599-606. https://doi.org/10.1158/0008-5472.CAN-05-0201
  11. Cheng YW, Shawber C, Fau - Notterman D, et al (2006). Multiplexed profiling of candidate genes for CpG island methylation status using a flexible PCR/LDR/Universal Array assay. Genome Res, 16, 282-9.
  12. Chuang SM, Chen L, Lambertson D, et al (2005). Proteasomemediated degradation of cotranslationally damaged proteins involves translation elongation factor 1A. Mol Cell Biol, 25, 403-13. https://doi.org/10.1128/MCB.25.1.403-413.2005
  13. Dapas B, Tell G, Scaloni A, et al (2003). Identification of different isoforms of eEF1A in the nuclear fraction of human T-lymphoblastic cancer cell line specifically binding to aptameric cytotoxic GT oligomers. Eur J Biochem, 270, 3251-62. https://doi.org/10.1046/j.1432-1033.2003.03713.x
  14. Ehrlich M (2002). DNA methylation in cancer: too much, but also too little. Oncogene, 12, 5400-13.
  15. Herman JG, Graff JR, Myohanen S, et al (1996). Methylationspecific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A, 93, 9821-6. https://doi.org/10.1073/pnas.93.18.9821
  16. Jones PA, Baylin SB (2007). The epigenomics of cancer. Cell, 128, 683-92. https://doi.org/10.1016/j.cell.2007.01.029
  17. Lamberti A, Caraglia M, Longo O, et al (2004). The translation elongation factor 1A in tumorigenesis, signal transduction and apoptosis: review article. Amino Acids, 26, 443-8.
  18. Locker GY, Hamilton S, Harris J, et al (2006). ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol, 24, 5313-27. https://doi.org/10.1200/JCO.2006.08.2644
  19. Maeda H, Miyajima N, Fau - Kano S, et al (2009). Ubiquitinconjugating enzyme UBE2Q2 suppresses cell proliferation and is down-regulated in recurrent head and neck cancer. Mol Cancer Res, 7, 1553-62. https://doi.org/10.1158/1541-7786.MCR-08-0543
  20. Mokarram P, Naghibalhossaini F, Fau - Saberi Firoozi M, et al (2008). Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status. World J Gastroentrol, 14, 3662-71. https://doi.org/10.3748/wjg.14.3662
  21. Nelson RL, Persky V, Turyk M (1999). Determination of factors responsible for the declining incidence of colorectal cancer. Dis Colon Rectum, 42, 741-52. https://doi.org/10.1007/BF02236929
  22. Nikseresht M, Seghatoleslam A, Fau - Monabati A, et al (2010). Overexpression of the novel human gene, UBE2Q2, in breast cancer. Cancer Genet Cytogenet, 197, 101-6. https://doi.org/10.1016/j.cancergencyto.2009.11.020
  23. Seghatoleslam A, Bozorg-Ghalati F, Monabati A, et al (2014). UBE2Q1, as a Down Regulated Gene in Pediatric Acute Lymphoblastic Leukemia. int j mol cell med, 3, 95-101.
  24. Seghatoleslam A, Monabati A, Fau - Bozorg-Ghalati F, et al (2012a). Expression of UBE2Q2, a putative member of the ubiquitin-conjugating enzyme family in pediatric acute lymphoblastic leukemia. Arch Iran Med, 15, 352-5.
  25. Seghatoleslam A, Nikseresht M, Fau - Shafiee SM, et al (2012b). Expression of the novel human gene, UBE2Q1, in breast tumors. Mol Biol Rep, 39.
  26. Seghatoleslam A, Zambrano A, Fau - Millon R, et al (2006). Analysis of a novel human gene, LOC92912, over-expressed in hypopharyngeal tumours. Biochem Biophys Acta, 6.
  27. Shafiee SM, Seghatoleslam A, Nikseresht M, et al (2013). UBE2Q1 expression in human colorectal tumors and cell lines. Mol Biol Rep, 40, 7045-51. https://doi.org/10.1007/s11033-013-2824-8
  28. Shafiee SM, Seghatoleslam A, Nikseresht M, et al (2014). Expression Status of UBE2Q2 in Colorectal Primary Tumors and Cell Lines. Iran J Med Sci, 39, 196-202.
  29. Shah R, Jones E, Vidart V, et al (2014). Biomarkers for early detection of colorectal cancer and polyps: systematic review. Cancer Epidemiol Biomarkers Prev, 23, 1712-28. https://doi.org/10.1158/1055-9965.EPI-14-0412
  30. Srivastava S, Shahi UP, Dibya A, et al (2014). Distribution of HPV genotypes and involvement of risk factors in cervical lesions and invasive cervical cancer: a study in an indian population. Int J Mol Cell Med, 3, 61-73.
  31. Suzuki H, Toyota M, Fau - Sato H, et al (2006). Roles and causes of abnormal DNA methylation in gastrointestinal cancers. Asian Pac J Cancer Prev, 7, 177-85.
  32. Urano T, Saito T, Tsukui T, et al (2002). Efp targets 14-3-3 sigma for proteolysis and promotes breast tumour growth. Nature, 417, 871-5. https://doi.org/10.1038/nature00826
  33. van Wijk SJ, Timmers HT (2010). The family of ubiquitinconjugating enzymes (E2s): deciding between life and death of proteins. Faseb J, 24, 981-93. https://doi.org/10.1096/fj.09-136259
  34. Voutsadakis IA (2008). The ubiquitin-proteasome system in colorectal cancer. Biochem Biophys Acta, 1782, 800-8.
  35. Wajed SA, Laird PW, DeMeester TR (2001). DNA methylation: an alternative pathway to cancer. Ann Surg, 234, 10-20. https://doi.org/10.1097/00000658-200107000-00003
  36. Wan C, Chen J, Fau - Hu B, et al (2014). Downregulation of UBE2Q1 is associated with neuronal apoptosis in rat brain cortex following traumatic brain injury. J Neurosci Res, 92, 1-12. https://doi.org/10.1002/jnr.23305
  37. Weitz J, Koch M, Debus J, et al (2005). Colorectal cancer. Lancet, 365, 153-65. https://doi.org/10.1016/S0140-6736(05)17706-X
  38. Zhu S, Yao F, Fau - Li WH, et al (2013). PKC?-dependent activation of the ubiquitin proteasome system is responsible for high glucose-induced human breast cancer MCF-7 cell proliferation, migration and invasion. Asian Pac J Cancer Prev, 14.

Cited by

  1. Epigenetic biomarkers in colorectal cancer: premises and prospects pp.1366-5804, 2016, https://doi.org/10.1080/1354750X.2016.1252961