title: SPINT2 Deregulation in Prostate Carcinoma.
abstract: SPINT2 is a tumor suppressor gene that inhibits proteases implicated in cancer progression, like HGFA, hepsin and matriptase. Loss of SPINT2 expression in tumors has been associated with gene promoter hypermethylation; however, little is known about the mechanisms of SPINT2 deregulation in prostate cancer (PCa). We aimed to analyze SPINT2 expression levels and understand the possible regulation by SPINT2 promoter hypermethylation in PCa. In a cohort of 57 cases including non-neoplastic and PCa tissues, SPINT2 expression and promoter methylation was analyzed by immunohistochemistry and methylation-specific PCR, respectively. Methylation status of the SPINT2 promoter was also evaluated by bisulfite sequencing and 5-aza-2'-deoxycytidine treatment. Oncomine and TCGA databases were used to perform in silico PCa analysis of SPINT2 mRNA and methylation levels. A reduction in SPINT2 expression levels from non-neoplastic to PCa tissues was observed; however, none of the cases exhibited SPINT2 promoter methylation. Both bisulfite sequencing and 5-aza demonstrated that SPINT2 promoter is not methylated in PCa cells. Bioinformatics approaches did not show downregulation of SPINT2 at the mRNA level and, in corroboration with our results, SPINT2 promoter region is reported to be unmethylated. Our study suggests an involvement of SPINT2 in PCa tumorigenesis, probably in association with a post-translational regulation of SPINT2.
authors.affiliation: ICVS/3B’s– PT Government Associate Laboratory, Braga/Guimarães, Portugal (MSP, FP, MVP, RMR)
authors.forename: Márcia Santos
authors.initials: MS
authors.lastname: Pereira
authors.affiliation: Department of Pathology, Barretos Cancer Hospital, S. Paulo, Brazil (GCA)
authors.forename: Gisele Caravina
authors.initials: GC
authors.lastname: de Almeida
authors.affiliation: School of Health Sciences, University of Minho, Braga, Portugal (MSP, FP, MVP, RMR)|ICVS/3B’s– PT Government Associate Laboratory, Braga/Guimarães, Portugal (MSP, FP, MVP, RMR)
authors.forename: Filipe
authors.initials: F
authors.lastname: Pinto
authors.affiliation: School of Health Sciences, University of Minho, Braga, Portugal (MSP, FP, MVP, RMR)|ICVS/3B’s– PT Government Associate Laboratory, Braga/Guimarães, Portugal (MSP, FP, MVP, RMR)
authors.forename: Marta
authors.initials: M
authors.lastname: Viana-Pereira
authors.affiliation: School of Health Sciences, University of Minho, Braga, Portugal (MSP, FP, MVP, RMR)|ICVS/3B’s– PT Government Associate Laboratory, Braga/Guimarães, Portugal (MSP, FP, MVP, RMR)|Molecular Oncology Research Center ,Barretos Cancer Hospital, S. Paulo, Brazil(RMR)
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C109148:SPINT2 protein, human
keywords: SPINT2; methylation; prostate carcinoma