MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer

Sumei Wang, Do Youn Oh, Vasiliki Leventaki, Elias Drakos, Ronghua Zhang, Aysegul A. Sahin, Erika Resetkova, Mary Elizabeth Edgerton, Wanyin Wu, Francois X. Claret

Research output: Contribution to journalArticle

Abstract

Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. Evidence indicates that aberrant JAB1/CSN5 expression is associated with advanced tumor stage and poor prognosis in breast cancer. In this study, we evaluated expression of JAB1 in TNBC and potential mechanisms regulating this expression. We found that miR-17 expression was lower in TNBC than in normal breast tissue, and miR-17 expression in patients with TNBC was associated with a good prognosis. Furthermore, JAB1 expression was regulated by miR-17 in TNBC cells, and mice with miR-17-overexpressing tumors had less tumor growth and lower tumor JAB1 expression than control mice. We also demonstrated that miR-17 suppressed JAB1's oncogenic function, leading to tumor growth inhibition and sensitizing TNBC cells to chemotherapy treatment. JAB1 knockdown in TNBC cells mimicked the effect of miR-17 overexpression and led to significant decreases in cell proliferation, colony formation, and migration, increased p27 expression, and enhanced cisplatin sensitivity. Our findings suggest that miR-17 acts as a tumor suppressor by directly targeting JAB1 in TNBC; this may lead to novel therapeutic targets and strategies for treating TNBC patients.

Original languageEnglish
Pages (from-to)12-23
Number of pages12
JournalCancer Letters
Volume465
DOIs
StatePublished - 28 Nov 2019

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Triple Negative Breast Neoplasms
MicroRNAs
Neoplasms
Breast Neoplasms
Growth
Cisplatin
Breast
Cell Proliferation
Drug Therapy

Keywords

  • JAB1/CSN5
  • microRNA
  • Therapeutic target
  • Triple-negative breast cancer

Cite this

Wang, Sumei ; Oh, Do Youn ; Leventaki, Vasiliki ; Drakos, Elias ; Zhang, Ronghua ; Sahin, Aysegul A. ; Resetkova, Erika ; Edgerton, Mary Elizabeth ; Wu, Wanyin ; Claret, Francois X. / MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer. In: Cancer Letters. 2019 ; Vol. 465. pp. 12-23.
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abstract = "Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. Evidence indicates that aberrant JAB1/CSN5 expression is associated with advanced tumor stage and poor prognosis in breast cancer. In this study, we evaluated expression of JAB1 in TNBC and potential mechanisms regulating this expression. We found that miR-17 expression was lower in TNBC than in normal breast tissue, and miR-17 expression in patients with TNBC was associated with a good prognosis. Furthermore, JAB1 expression was regulated by miR-17 in TNBC cells, and mice with miR-17-overexpressing tumors had less tumor growth and lower tumor JAB1 expression than control mice. We also demonstrated that miR-17 suppressed JAB1's oncogenic function, leading to tumor growth inhibition and sensitizing TNBC cells to chemotherapy treatment. JAB1 knockdown in TNBC cells mimicked the effect of miR-17 overexpression and led to significant decreases in cell proliferation, colony formation, and migration, increased p27 expression, and enhanced cisplatin sensitivity. Our findings suggest that miR-17 acts as a tumor suppressor by directly targeting JAB1 in TNBC; this may lead to novel therapeutic targets and strategies for treating TNBC patients.",
keywords = "JAB1/CSN5, microRNA, Therapeutic target, Triple-negative breast cancer",
author = "Sumei Wang and Oh, {Do Youn} and Vasiliki Leventaki and Elias Drakos and Ronghua Zhang and Sahin, {Aysegul A.} and Erika Resetkova and Edgerton, {Mary Elizabeth} and Wanyin Wu and Claret, {Francois X.}",
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Wang, S, Oh, DY, Leventaki, V, Drakos, E, Zhang, R, Sahin, AA, Resetkova, E, Edgerton, ME, Wu, W & Claret, FX 2019, 'MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer', Cancer Letters, vol. 465, pp. 12-23. https://doi.org/10.1016/j.canlet.2019.08.016

MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer. / Wang, Sumei; Oh, Do Youn; Leventaki, Vasiliki; Drakos, Elias; Zhang, Ronghua; Sahin, Aysegul A.; Resetkova, Erika; Edgerton, Mary Elizabeth; Wu, Wanyin; Claret, Francois X.

In: Cancer Letters, Vol. 465, 28.11.2019, p. 12-23.

Research output: Contribution to journalArticle

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T1 - MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer

AU - Wang, Sumei

AU - Oh, Do Youn

AU - Leventaki, Vasiliki

AU - Drakos, Elias

AU - Zhang, Ronghua

AU - Sahin, Aysegul A.

AU - Resetkova, Erika

AU - Edgerton, Mary Elizabeth

AU - Wu, Wanyin

AU - Claret, Francois X.

PY - 2019/11/28

Y1 - 2019/11/28

N2 - Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. Evidence indicates that aberrant JAB1/CSN5 expression is associated with advanced tumor stage and poor prognosis in breast cancer. In this study, we evaluated expression of JAB1 in TNBC and potential mechanisms regulating this expression. We found that miR-17 expression was lower in TNBC than in normal breast tissue, and miR-17 expression in patients with TNBC was associated with a good prognosis. Furthermore, JAB1 expression was regulated by miR-17 in TNBC cells, and mice with miR-17-overexpressing tumors had less tumor growth and lower tumor JAB1 expression than control mice. We also demonstrated that miR-17 suppressed JAB1's oncogenic function, leading to tumor growth inhibition and sensitizing TNBC cells to chemotherapy treatment. JAB1 knockdown in TNBC cells mimicked the effect of miR-17 overexpression and led to significant decreases in cell proliferation, colony formation, and migration, increased p27 expression, and enhanced cisplatin sensitivity. Our findings suggest that miR-17 acts as a tumor suppressor by directly targeting JAB1 in TNBC; this may lead to novel therapeutic targets and strategies for treating TNBC patients.

AB - Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. Evidence indicates that aberrant JAB1/CSN5 expression is associated with advanced tumor stage and poor prognosis in breast cancer. In this study, we evaluated expression of JAB1 in TNBC and potential mechanisms regulating this expression. We found that miR-17 expression was lower in TNBC than in normal breast tissue, and miR-17 expression in patients with TNBC was associated with a good prognosis. Furthermore, JAB1 expression was regulated by miR-17 in TNBC cells, and mice with miR-17-overexpressing tumors had less tumor growth and lower tumor JAB1 expression than control mice. We also demonstrated that miR-17 suppressed JAB1's oncogenic function, leading to tumor growth inhibition and sensitizing TNBC cells to chemotherapy treatment. JAB1 knockdown in TNBC cells mimicked the effect of miR-17 overexpression and led to significant decreases in cell proliferation, colony formation, and migration, increased p27 expression, and enhanced cisplatin sensitivity. Our findings suggest that miR-17 acts as a tumor suppressor by directly targeting JAB1 in TNBC; this may lead to novel therapeutic targets and strategies for treating TNBC patients.

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KW - microRNA

KW - Therapeutic target

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