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

Mariana Brait Rodrigues De Oliveira, Shizhang Ling, Jatin K. Nagpal, Xiaofei Chang, Hannah Lui Park, Juna Lee, Jun Okamura, Keishi Yamashita, David Sidransky, Myoung Sook Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere44951
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 27 2012

Fingerprint

Cysteine Dioxygenase
Methylation
tumor suppressor genes
Tumor Suppressor Genes
methylation
cysteine
Tumors
Genes
promoter regions
neoplasms
Neoplasms
Tissue
decitabine
Cells
Cell growth
Cell culture
Colorectal Neoplasms
colorectal neoplasms
cell growth
cell lines

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cysteine Dioxygenase 1 Is a Tumor Suppressor Gene Silenced by Promoter Methylation in Multiple Human Cancers. / Brait Rodrigues De Oliveira, Mariana; Ling, Shizhang; Nagpal, Jatin K.; Chang, Xiaofei; Park, Hannah Lui; Lee, Juna; Okamura, Jun; Yamashita, Keishi; Sidransky, David; Kim, Myoung Sook.

In: PLoS One, Vol. 7, No. 9, e44951, 27.09.2012.

Research output: Contribution to journalArticle

Brait Rodrigues De Oliveira, Mariana ; Ling, Shizhang ; Nagpal, Jatin K. ; Chang, Xiaofei ; Park, Hannah Lui ; Lee, Juna ; Okamura, Jun ; Yamashita, Keishi ; Sidransky, David ; Kim, Myoung Sook. / Cysteine Dioxygenase 1 Is a Tumor Suppressor Gene Silenced by Promoter Methylation in Multiple Human Cancers. In: PLoS One. 2012 ; Vol. 7, No. 9.
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