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miR-888: A novel cancer-testis antigen that targets the progesterone receptor in endometrial cancer
Journal article   Open access   Peer reviewed

miR-888: A novel cancer-testis antigen that targets the progesterone receptor in endometrial cancer

Adriann M Hovey, Eric J Devor, Donghai Dai, Kristina W Thiel, Kimberly K Leslie, Patrick J Breheny and Sarah L Mott
Translational Oncology, Vol.8(2), pp.85-96
2015
DOI: 10.1016/j.tranon.2015.02.001
PMID: 25926074
url
https://doi.org/10.1016/j.tranon.2015.02.001View
Published (Version of record) Open Access

Abstract

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.

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