Cancer-testis (CT) antigens are a large family of genes that are selectively expressed in human testis germ cells, overexpressed in a variety of tumors and predominantly located on the X chromosome. 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 and minimal or absent in all other examined tissues. In situ hybridization localized miR-888 expression specifically to the early stages of sperm development within the testes. Using The Cancer Genome Atlas database, we discovered that miR-888 was predominately expressed in endometrial tumors, with a significant association to high-grade tumors and increased percent invasion. In a separate panel of endometrial tumor specimens, we validated overexpression of miR-888 by real-time polymerase chain reaction. In addition, miR-888 expression was highest in endometrial carcinosarcoma, a rare and aggressive type of endometrial tumor. Moreover, we identified the progesterone receptor (PR), a potent endometrial tumor suppressor, as a direct target of miR-888. These data define miR-888 as the first miRNA CT antigen and a potential mediator of an aggressive endometrial tumor phenotype through down-regulation of PR.

睾丸癌（CT）抗原是一大类基因，它们在人的睾丸生殖细胞中选择性表达，在多种肿瘤中过表达，并且主要位于X染色体上。迄今为止，所有已知的CT抗原都是蛋白质编码基因。在这里，我们确定miR-888为第一个具有CT抗原特征的miRNA。在一组21种正常人类组织中，miR-888在睾丸中的表达很高，而在所有其他检查过的组织中则很少或没有。原位杂交将miR-888表达专门定位于睾丸内精子发育的早期阶段。使用癌症基因组图谱数据库，我们发现miR-888主要在子宫内膜肿瘤中表达，与高级别肿瘤和增加的侵袭百分率显着相关。在单独的一组子宫内膜肿瘤标本中，我们通过实时聚合酶链反应验证了miR-888的过表达。此外，miR-888在子宫内膜癌肉瘤中是最高的，子宫内膜癌肉瘤是一种罕见的侵袭性子宫内膜肿瘤。此外，我们确定孕激素受体（PR），一种有效的子宫内膜肿瘤抑制剂，是miR-888的直接靶标。这些数据将miR-888定义为第一个miRNA CT抗原，并且是通过PR下调而侵袭性子宫内膜肿瘤表型的潜在介体。