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Background  Posttranslational protein modifications are known to modulate key biological processes like proliferation and apoptosis. Accumulating evidence shows that ST6GAL1, an enzyme that catalyzes the transfer of sialic acid onto galactose-containing substrates, is aberrantly expressed in various cancers and may affect cell motility and invasion. This is the first study to describe ST6GAL1 expression and regulation in human bladder cancer.    Methods   ST6GAL1  mRNA expression levels in human cell lines (UROtsa, RT4, RT112 and J82) and tissue samples (n = 15 normal urothelium (NU), n = 13 papillary non-invasive tumors (pTa), n = 12 carcinoma in situ (CIS), n = 26 muscle invasive tumors (pT2-4)) were assessed using real-time PCR. In addition, ST6GAL1 protein expression was evaluated using immunohistochemistry. Promoter methylation analysis was performed using methylation-specific PCR (MSP) in cell lines (n = 4) and patient samples (n = 23 NU, n = 12 CIS, n = 29 pTa, n = 41 pT2-4). Epigenetic  ST6GAL1  gene silencing was confirmed by  in vitro  demethylation of bladder cell lines. Data were validated by analysis of an independent bladder tumor data set (n = 184) based on  The Cancer Genome Atlas  (TCGA) portal.    Results  Semi-quantitative  ST6GAL1  real-time PCR expression analysis showed two distinct trends: In muscle-invasive tumors  ST6GAL1  expression was downregulation by 2.7-fold, while papillary non-invasive tumors showed an increased  ST6GAL1  mRNA expression compared to normal urothelium.  ST6GAL1  loss in muscle-invasive tumors was associated with increasing invasiveness. On the protein level, 69.2% (n = 45/65) of all tumors showed a weak ST6GAL1 protein staining (IRS ≤ 4) while 25.6% (16/65) exhibited a complete loss (IRS = 0) of ST6GAL1 protein. Tumor-specific DNA methylation of the  ST6GAL1  promoter region was frequently found in pT2-4 tumors (53.6% (22/41)), whereas only 13.8% (4/29) of pTa tumors showed  ST6GAL1  promoter methylation .  Normal urothelium remained unmethylated. Importantly, we significantly revealed an inverse correlation between  ST6GAL1  mRNA expression and  ST6GAL1  promoter merthylation in primary bladder cancer. These findings were clearly verified by the TCGA public data set and  in vitro  demethylation assays functionally confirmed  ST6GAL1  promoter methylation as a potential regulatory factor for  ST6GAL1  gene silencing.    Conclusions  Our study characterizes for the first time ST6GAL1 expression loss caused by aberrant  ST6GAL1  promoter methylation potentially indicating a tumor suppressive role in bladder carcinogenesis.    Electronic supplementary material  The online version of this article (doi:10.1186/1471-2407-14-901) contains supplementary material, which is available to authorized users.

Epigenetic inactivation of ST6GAL1 in human bladder cancer