Abstract
Abstract Cancer-testis (CT) antigens are a large family of genes that are exclusively expressed in human testes and are typically located on the X chromosome and part of multicopy gene families. Importantly, CT antigens are overexpressed in a variety of tumors. To date, all known CT antigens are protein-coding genes. Here we identify miR-888 as the first miRNA with features characteristic of a CT antigen. In a panel of 21 normal human tissues, miR-888 expression was high in testes, but minimal or absent in all other tissues. Analysis of cancer cell lines demonstrated expression of miR-888 in endometrial cancer cells, but not in choriocarcinoma, breast, ovarian or prostate cancer cells. In endometrial patient tumor specimens, miR-888 was 8-fold overexpressed relative to benign endometrium (p < 0.01). In addition, expression of miR-888 was highest in endometrial carcinosarcomas (fold change = 22, p < 0.01), a rare and aggressive type of endometrial tumor. Analysis of The Cancer Genome Atlas database revealed that miR-888 expression is significantly associated with high stage and grade endometrial tumors, which has also been observed for many other CT antigens. Furthermore, the miR-888 gene is part of a multicopy gene family on the X chromosome and evolved recently in primates through gene duplication. Therefore, we classify miR-888 as the first miRNA CT antigen and hypothesize that other miRNAs located on the X chromosome may also function as CT antigens. These findings have the potential to advance understanding of cancer-testis genes, their evolution and what role they play in testis and cancer biology. Note: This abstract was not presented at the meeting. Citation Format: Adriann M. Hovey, Eric J. Devor, Donghai Dai, Kimberly K. Leslie. Identification of miR-888 as the first miRNA cancer-testis antigen. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5236. doi:10.1158/1538-7445.AM2014-5236
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