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miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2
SIMPLE SUMMARY: ATPase family AAA domain-containing protein 2 (ATAD2) overexpression is associated with poor survival and disease recurrence in multiple cancers. The current study aimed to investigate the expression and function of ATAD2 in breast cancer. Our results showed that ATAD2 expression was...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497224/ https://www.ncbi.nlm.nih.gov/pubmed/36139505 http://dx.doi.org/10.3390/cancers14184345 |
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author | Hwang, Yo Sep Park, Eun Sun Oh, Byung Moo Uhm, Tae Gi Yoon, Suk Ran Park, Jong-Lyul Cho, Hee Jun Lee, Hee Gu |
author_facet | Hwang, Yo Sep Park, Eun Sun Oh, Byung Moo Uhm, Tae Gi Yoon, Suk Ran Park, Jong-Lyul Cho, Hee Jun Lee, Hee Gu |
author_sort | Hwang, Yo Sep |
collection | PubMed |
description | SIMPLE SUMMARY: ATPase family AAA domain-containing protein 2 (ATAD2) overexpression is associated with poor survival and disease recurrence in multiple cancers. The current study aimed to investigate the expression and function of ATAD2 in breast cancer. Our results showed that ATAD2 expression was upregulated in human breast cancer tissues and cell lines, while ATAD2 knockdown inhibited the proliferation, migration, and invasion of breast cancer cells. Moreover, we provide evidence suggesting that miR-302 directly targets ATAD2 and thus modulates cancer cell proliferation, migration, and invasion in vitro. Moreover, ATAD2 overexpression rescued the inhibition of tumor growth caused by miR-302 in xenograft mice. These findings indicate that miR-302 plays a crucial role in inhibiting the malignant phenotypes of breast cancer cells by targeting ATAD2. ABSTRACT: Breast cancer is the most common malignant tumor in women. The ATPase family AAA domain-containing protein 2 (ATAD2) contains an ATPase domain and a bromodomain, and is abnormally expressed in various human cancers, including breast cancer. However, the molecular mechanisms underlying the regulation of ATAD2 expression in breast cancer remain unclear. This study aimed to investigate the expression and function of ATAD2 in breast cancer. We found that ATAD2 was highly expressed in human breast cancer tissues and cell lines. ATAD2 depletion via RNA interference inhibited the proliferation, migration, and invasive ability of the SKBR3 and T47D breast cancer cell lines. Furthermore, Western blot analysis and luciferase assay results revealed that ATAD2 is a putative target of miR-302. Transfection with miR-302 mimics markedly reduced cell migration and invasion. These inhibitory effects of miR-302 were restored by ATAD2 overexpression. Moreover, miR-302 overexpression in SKBR3 and T47D cells suppressed tumor growth in the xenograft mouse model. However, ATAD2 overexpression rescued the decreased tumor growth seen after miR-302 overexpression. Our findings indicate that miR-302 plays a prominent role in inhibiting the cancer cell behavior associated with tumor progression by targeting ATAD2, and could thus be a valuable target for breast cancer therapy. |
format | Online Article Text |
id | pubmed-9497224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94972242022-09-23 miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2 Hwang, Yo Sep Park, Eun Sun Oh, Byung Moo Uhm, Tae Gi Yoon, Suk Ran Park, Jong-Lyul Cho, Hee Jun Lee, Hee Gu Cancers (Basel) Article SIMPLE SUMMARY: ATPase family AAA domain-containing protein 2 (ATAD2) overexpression is associated with poor survival and disease recurrence in multiple cancers. The current study aimed to investigate the expression and function of ATAD2 in breast cancer. Our results showed that ATAD2 expression was upregulated in human breast cancer tissues and cell lines, while ATAD2 knockdown inhibited the proliferation, migration, and invasion of breast cancer cells. Moreover, we provide evidence suggesting that miR-302 directly targets ATAD2 and thus modulates cancer cell proliferation, migration, and invasion in vitro. Moreover, ATAD2 overexpression rescued the inhibition of tumor growth caused by miR-302 in xenograft mice. These findings indicate that miR-302 plays a crucial role in inhibiting the malignant phenotypes of breast cancer cells by targeting ATAD2. ABSTRACT: Breast cancer is the most common malignant tumor in women. The ATPase family AAA domain-containing protein 2 (ATAD2) contains an ATPase domain and a bromodomain, and is abnormally expressed in various human cancers, including breast cancer. However, the molecular mechanisms underlying the regulation of ATAD2 expression in breast cancer remain unclear. This study aimed to investigate the expression and function of ATAD2 in breast cancer. We found that ATAD2 was highly expressed in human breast cancer tissues and cell lines. ATAD2 depletion via RNA interference inhibited the proliferation, migration, and invasive ability of the SKBR3 and T47D breast cancer cell lines. Furthermore, Western blot analysis and luciferase assay results revealed that ATAD2 is a putative target of miR-302. Transfection with miR-302 mimics markedly reduced cell migration and invasion. These inhibitory effects of miR-302 were restored by ATAD2 overexpression. Moreover, miR-302 overexpression in SKBR3 and T47D cells suppressed tumor growth in the xenograft mouse model. However, ATAD2 overexpression rescued the decreased tumor growth seen after miR-302 overexpression. Our findings indicate that miR-302 plays a prominent role in inhibiting the cancer cell behavior associated with tumor progression by targeting ATAD2, and could thus be a valuable target for breast cancer therapy. MDPI 2022-09-06 /pmc/articles/PMC9497224/ /pubmed/36139505 http://dx.doi.org/10.3390/cancers14184345 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hwang, Yo Sep Park, Eun Sun Oh, Byung Moo Uhm, Tae Gi Yoon, Suk Ran Park, Jong-Lyul Cho, Hee Jun Lee, Hee Gu miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2 |
title | miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2 |
title_full | miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2 |
title_fullStr | miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2 |
title_full_unstemmed | miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2 |
title_short | miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2 |
title_sort | mir-302 suppresses the proliferation, migration, and invasion of breast cancer cells by downregulating atad2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497224/ https://www.ncbi.nlm.nih.gov/pubmed/36139505 http://dx.doi.org/10.3390/cancers14184345 |
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