Tumor Biology

, Volume 37, Issue 2, pp 1707–1714 | Cite as

CpG methylation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) and P53 mutation pattern in sporadic colorectal cancer

  • Rania Abdelmaksoud-Dammak
  • Amena Saadallah-Kallel
  • Imen Miladi-Abdennadher
  • Lobna Ayedi
  • Abdelmajid Khabir
  • Tahia Sallemi-Boudawara
  • Mounir Frikha
  • Jamel Daoud
  • Raja Mokdad-Gargouri
Original Article

Abstract

The ubiquitin-proteasome system plays an essential regulatory role in various cellular processes. Besides its involvement in normal cellular functions, the alteration of proteasomal activity contributes to the pathological states of several clinical disorders, including cancer. Aberrant methylation of the CpG islands has been reported as an alternative way to inactivate gene expression involved in the ubiquitination process and thus protein degradation in tumor tissues. In this study, we aimed to determine the CpG methylation pattern of the UCHL1 promoter, as well as the mutation spectrum and the expression pattern of P53 in sporadic colorectal cancer (CRC) from Tunisian patients. We found that UCHL1 was methylated in 68.57 % and correlated significantly with lymph node metastasis (P = 0.029) and transcriptional silencing in tumor tissues (P = 0.013). Mutation screening of exons 5–9 of P53 showed that 42.85 % of cases harbor somatic mutation and are positively correlated with the methylated pattern of UCHL1 (P = 0.001). Furthermore, cytoplasmic accumulation of P53 was strongly associated with the unmethylated UCHL1 profile (P = 0.006), supporting the relationship between these two proteins in CRC.

Keywords

UCHL1 CpG methylation Colon cancer Transcriptional silencing P53 

Notes

Acknowledgments

This work was supported by a grant from the Tunisian Ministry of Higher Education and Scientific Research. We thank the technician from the “Department of Analysis-CBS” for DNA sequencing.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Rania Abdelmaksoud-Dammak
    • 1
  • Amena Saadallah-Kallel
    • 1
  • Imen Miladi-Abdennadher
    • 1
  • Lobna Ayedi
    • 2
  • Abdelmajid Khabir
    • 2
  • Tahia Sallemi-Boudawara
    • 2
  • Mounir Frikha
    • 3
  • Jamel Daoud
    • 4
  • Raja Mokdad-Gargouri
    • 1
  1. 1.Center of Biotechnology of Sfax, Laboratory of Biomass Valorisation and Production of Eukaryotic ProteinsUniversity of SfaxSfaxTunisia
  2. 2.Department of AnatomopathologyHabib Bourguiba HospitalSfaxTunisia
  3. 3.Department of Medical OncologyHabib Bourguiba HospitalSfaxTunisia
  4. 4.Department of RadiotherapyHabib Bourguiba HospitalSfaxTunisia

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