title: PAPILLARY THYROID CANCER IS CHARACTERIZED BY ALTERED EXPRESSION OF GENES INVOLVED IN THE SUMOYLATION PROCESS.
abstract: Small Ubiquitinlike MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tuccilli
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Baldini
authors.affiliation: Department of Surgical Sciences, Sapienza University of Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sorrenti
authors.affiliation: Department of Radiology, Oncology and Pathological Anatomy, Sapienza University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Di Gioia
authors.affiliation: Department of Radiology, Oncology and Pathological Anatomy, Sapienza University of Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Bosco
authors.affiliation: Department of Radiology, Oncology and Pathological Anatomy, Sapienza University of Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Ascoli
authors.affiliation: Department of Medicine, University of Padua, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Mian
authors.affiliation: Department of Medicine, University of Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Barollo
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rendina
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Coccaro
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pepe
authors.affiliation: Department of Surgical Sciences, Sapienza University of Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Catania
authors.affiliation: Department of Surgery Pietro Valdoni, Sapienza University of Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bononi
authors.affiliation: Department of Surgical Sciences, Sapienza University of Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tartaglia
authors.affiliation: Department of Surgical Sciences, Sapienza University of Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: De Antoni
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Armiento
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ulisse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002291:Carcinoma, Papillary; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D058207:Sumoylation; D015996:Survival Rate; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins