title: CpG methylation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) and P53 mutation pattern in sporadic colorectal cancer.
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.
authors: Center of Biotechnology of Sfax, Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins, University of Sfax, Sfax, Tunisia.
authors: Rania
authors: R
authors: Abdelmaksoud-Dammak
authors: Center of Biotechnology of Sfax, Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins, University of Sfax, Sfax, Tunisia.
authors: Amena
authors: A
authors: Saadallah-Kallel
authors: Center of Biotechnology of Sfax, Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins, University of Sfax, Sfax, Tunisia.
authors: Imen
authors: I
authors: Miladi-Abdennadher
authors: Department of Anatomopathology, Habib Bourguiba Hospital, Sfax, Tunisia.
authors: Lobna
authors: L
authors: Ayedi
authors: Department of Anatomopathology, Habib Bourguiba Hospital, Sfax, Tunisia.
authors: Abdelmajid
authors: A
authors: Khabir
authors: Department of Anatomopathology, Habib Bourguiba Hospital, Sfax, Tunisia.
authors: Tahia
authors: T
authors: Sallemi-Boudawara
authors: Department of Medical Oncology, Habib Bourguiba Hospital, Sfax, Tunisia.
authors: Mounir
authors: M
authors: Frikha
authors: Department of Radiotherapy, Habib Bourguiba Hospital, Sfax, Tunisia.
authors: Jamel
authors: J
authors: Daoud
authors: Center of Biotechnology of Sfax, Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins, University of Sfax, Sfax, Tunisia. raja.gargouri@cbs.rnrt.tn.
authors: Raja
authors: R
authors: Mokdad-Gargouri
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014416:Tunisia; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Colon cancer; CpG methylation; P53; Transcriptional silencing; UCHL1