SPINT2 deregulation in prostate carcinoma

• Published in: The journal of histochemistry and cytochemistry Vol. 64; no. 1; pp. 32 - 41
• Main Authors: Pereira, M. S., de Almeida, G. C., Pinto, F., Viana-Pereira, M., Reis, R. M.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2016
• Subjects: Aged; Cell Line, Tumor; Ciências da Saúde; Ciências Médicas; Computational Biology; Gene Expression Regulation, Neoplastic; Humans; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Methylation; Middle Aged; Prostate carcinoma; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science & Technology; SPINT2; prostate carcinoma; methylation; SPINT2
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1369/0022155415612874

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 nonneoplastic 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. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the ICVS internal research funds of participating authors and by FCT project, ref. PTDC/SAUONC/115513/2009. F.P. received fellowship from the FCT, ref. SFRH/BD/81369/2011 and M.VP from the ON.2 SR&TD Integrated Program (N-01-01-01-24-01-07), ref. UMINHO/ BPD/36/2013.