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...
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Series: | Translational Oncology |
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doaj-ed54ef008e0d4b50b271743fed8ca0e22020-11-25T02:32:43ZengElsevierTranslational Oncology1936-52331944-71242015-04-0182859610.1016/j.tranon.2015.02.001miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial CancerAdriann M. Hovey0Eric J. Devor1Patrick J. Breheny2Sarah L. Mott3Donghai Dai4Kristina W. Thiel5Kimberly K. Leslie6Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USADepartment of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USADepartment of Biostatistics, University of Iowa, Iowa City, IA, USAHolden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USADepartment of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USADepartment of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USADepartment of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USACancer-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.http://www.sciencedirect.com/science/article/pii/S1936523315000054 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adriann M. Hovey Eric J. Devor Patrick J. Breheny Sarah L. Mott Donghai Dai Kristina W. Thiel Kimberly K. Leslie |
spellingShingle |
Adriann M. Hovey Eric J. Devor Patrick J. Breheny Sarah L. Mott Donghai Dai Kristina W. Thiel Kimberly K. Leslie miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer Translational Oncology |
author_facet |
Adriann M. Hovey Eric J. Devor Patrick J. Breheny Sarah L. Mott Donghai Dai Kristina W. Thiel Kimberly K. Leslie |
author_sort |
Adriann M. Hovey |
title |
miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer |
title_short |
miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer |
title_full |
miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer |
title_fullStr |
miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer |
title_full_unstemmed |
miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer |
title_sort |
mir-888: a novel cancer-testis antigen that targets the progesterone receptor in endometrial cancer |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 1944-7124 |
publishDate |
2015-04-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S1936523315000054 |
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