Cytoglobin (CYGB), a new member of the globin family, remains to be characterized. To assess its expression in human malignancies, we screened a number of cell lines originated from many tissues, and found that several, but not all, melanoma cell lines expressed CYGB mRNA and protein at much higher levels than cells of other origins. Melanocytes, the primary origin of melanoma, also expressed CYGB at a high level. Bisulfite-modified genomic sequencing revealed that several melanoma cell lines that abrogated CYGB expression were found to be epigenetically regulated by hypermethylation in the promoter region of CYGB gene. The RNAi-mediated knockdown of the CYGB transcript in CYGB expression-positive melanoma cell lines resulted in increased proliferation in vitro and in vivo. Flow cytometric analysis using an indicator of reactive oxygen species (ROS) revealed that the CYGB knockown enhanced the cellular ROS level, which may be involved in the antiproliferative effect of CYGB. Thus, CYGB appears to play a tumor suppressive role as a ROS regulator, and its epigenetic silencing, as observed in CYGB expression-negative melanoma cell lines, might function as an alternative pathway in the melanocyte-to-melanoma transition.

Citation Format: Yoshihiko Fujita, Satoshi Koinuma, Marco De Velasco, Bolz Jan, Yosuke Togashi, Masato Terashima, Hidetoshi Hayashi, Takuya Matsuo, Kazuto Nishio. Melanoma transition is frequently accompanied by a loss of cytoglobin, a putative tumor suppressor, in melanocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4958. doi:10.1158/1538-7445.AM2015-4958

©2015 American Association for Cancer Research.
2015