miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer.
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.
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
Adriann M
AM
Hovey
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
Eric J
EJ
Devor
Department of Biostatistics, University of Iowa, Iowa City, IA, USA.
Patrick J
PJ
Breheny
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
Sarah L
SL
Mott
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
Donghai
D
Dai
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
Kristina W
KW
Thiel
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. Electronic address: kimberly-leslie@uoiwa.edu.
Kimberly K
KK
Leslie