Cargando…
ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation
The oncogene ATPase family AAA domain-containing protein 2 (ATAD2) has been demonstrated to promote malignancy in a number of different types of tumor; however, its expression and role in ovarian cancer (OC) remain unknown. In the present study, it was demonstrated that ATAD2 acts as both a marker a...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910177/ https://www.ncbi.nlm.nih.gov/pubmed/31746426 http://dx.doi.org/10.3892/ijo.2019.4913 |
_version_ | 1783479060163198976 |
---|---|
author | Liu, Qun Liu, Heshu Li, Lina Dong, Xiaomei Ru, Xiaoli Fan, Xiana Wen, Tao Liu, Jian |
author_facet | Liu, Qun Liu, Heshu Li, Lina Dong, Xiaomei Ru, Xiaoli Fan, Xiana Wen, Tao Liu, Jian |
author_sort | Liu, Qun |
collection | PubMed |
description | The oncogene ATPase family AAA domain-containing protein 2 (ATAD2) has been demonstrated to promote malignancy in a number of different types of tumor; however, its expression and role in ovarian cancer (OC) remain unknown. In the present study, it was demonstrated that ATAD2 acts as both a marker and a driver of cell proliferation in OC. Immunohistochemistry (IHC) and bioinformatics analyses were used to evaluate ATAD2 expression in OC, and multi-omics integrated analyses were used to dissect which factor resulted in its upregulation. Multiplex IHC assay was used to reveal the specific expression of ATAD2 in proliferating OC cells. CRISPR-Cas9-mediated gene editing was performed to investigate the effect of ATAD2 deletion on OC proliferation. The results demonstrated that ATAD2 is elevated in primary OC tissues compared with the adjacent normal tissue and metastases from the stomach. Genetic copy number amplification is a primary cause resulting in upregulation of ATAD2, and this was most frequently observed in OC. High ATAD2 expression was associated with advanced progression and predicted an unfavorable prognosis. ATAD2 could be used to identify cases of OC with a high proliferation signature and could label proliferating cells in OC. CRISPR-Cas9-mediated ATAD2 deletion resulted in a significant decrease in both cell proliferation and colony formation ability. Mechanistically, ATAD2-knockdown resulted in deactivation of the mitogen-activated protein kinase (MAPK) pathways, particularly the JNK-MAPK pathway, resulting in suppression of proliferation. Collectively, the data from the present study demonstrated that the ATD2 gene was frequently amplified and protein expression levels were upregulated in OC. Therefore, ATAD2 may serve as an attractive diagnostic and prognostic OC marker, which may be used to identify patients with primary OC, whom are most likely to benefit from ATAD2 gene-targeted proliferation intervention therapies. |
format | Online Article Text |
id | pubmed-6910177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-69101772019-12-18 ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation Liu, Qun Liu, Heshu Li, Lina Dong, Xiaomei Ru, Xiaoli Fan, Xiana Wen, Tao Liu, Jian Int J Oncol Articles The oncogene ATPase family AAA domain-containing protein 2 (ATAD2) has been demonstrated to promote malignancy in a number of different types of tumor; however, its expression and role in ovarian cancer (OC) remain unknown. In the present study, it was demonstrated that ATAD2 acts as both a marker and a driver of cell proliferation in OC. Immunohistochemistry (IHC) and bioinformatics analyses were used to evaluate ATAD2 expression in OC, and multi-omics integrated analyses were used to dissect which factor resulted in its upregulation. Multiplex IHC assay was used to reveal the specific expression of ATAD2 in proliferating OC cells. CRISPR-Cas9-mediated gene editing was performed to investigate the effect of ATAD2 deletion on OC proliferation. The results demonstrated that ATAD2 is elevated in primary OC tissues compared with the adjacent normal tissue and metastases from the stomach. Genetic copy number amplification is a primary cause resulting in upregulation of ATAD2, and this was most frequently observed in OC. High ATAD2 expression was associated with advanced progression and predicted an unfavorable prognosis. ATAD2 could be used to identify cases of OC with a high proliferation signature and could label proliferating cells in OC. CRISPR-Cas9-mediated ATAD2 deletion resulted in a significant decrease in both cell proliferation and colony formation ability. Mechanistically, ATAD2-knockdown resulted in deactivation of the mitogen-activated protein kinase (MAPK) pathways, particularly the JNK-MAPK pathway, resulting in suppression of proliferation. Collectively, the data from the present study demonstrated that the ATD2 gene was frequently amplified and protein expression levels were upregulated in OC. Therefore, ATAD2 may serve as an attractive diagnostic and prognostic OC marker, which may be used to identify patients with primary OC, whom are most likely to benefit from ATAD2 gene-targeted proliferation intervention therapies. D.A. Spandidos 2019-11-14 /pmc/articles/PMC6910177/ /pubmed/31746426 http://dx.doi.org/10.3892/ijo.2019.4913 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Liu, Qun Liu, Heshu Li, Lina Dong, Xiaomei Ru, Xiaoli Fan, Xiana Wen, Tao Liu, Jian ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation |
title | ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation |
title_full | ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation |
title_fullStr | ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation |
title_full_unstemmed | ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation |
title_short | ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation |
title_sort | atad2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910177/ https://www.ncbi.nlm.nih.gov/pubmed/31746426 http://dx.doi.org/10.3892/ijo.2019.4913 |
work_keys_str_mv | AT liuqun atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation AT liuheshu atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation AT lilina atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation AT dongxiaomei atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation AT ruxiaoli atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation AT fanxiana atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation AT wentao atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation AT liujian atad2predictspooroutcomesinpatientswithovariancancerandisamarkerofproliferation |