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The human  cysteine dioxygenase 1  ( CDO1 ) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinate, and plays a key role in taurine biosynthesis. In our search for novel methylated gene promoters, we have analyzed differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of 5-aza-2′-deoxycytidine. Among the genes identified, the  CDO1  promoter was found to be differentially methylated in primary CRC tissues with high frequency compared to normal colon tissues. In addition, a statistically significant difference in the frequency of  CDO1  promoter methylation was observed between primary normal and tumor tissues derived from breast, esophagus, lung, bladder and stomach. Downregulation of  CDO1  mRNA and protein levels were observed in cancer cell lines and tumors derived from these tissue types. Expression of  CDO1  was tightly controlled by promoter methylation, suggesting that promoter methylation and silencing of  CDO1  may be a common event in human carcinogenesis. Moreover, forced expression of full-length  CDO1  in human cancer cells markedly decreased the tumor cell growth in an  in vitro  cell culture and/or an  in vivo  mouse model, whereas knockdown of  CDO1  increased cell growth in culture. Our data implicate  CDO1  as a novel tumor suppressor gene and a potentially valuable molecular marker for human cancer.

Cysteine Dioxygenase 1 Is a Tumor Suppressor Gene Silenced by Promoter Methylation in Multiple Human Cancers