@article{53a84a010c3148d3b44fc03909f1bee8,
title = "MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer",
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, Therapeutic target, Triple-negative breast cancer, microRNA",
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.}",
note = "Funding Information: D-Y Oh reports receiving grants from AstraZeneca, Array and Mogam (all outside of this work) and is a consultant/advisory for AstraZeneca, Merck Serono, Bayer, Novartis, Genentech, Abbvie, Halozyme, ASLAN, BMS, ONO (outside this work), No potential conflicts of interest were disclosed by the other authors.The authors want to thank J.A. Pietenpol for sharing data and L.L. Russell from The University of Texas MD Anderson Cancer Center's Scientific Publication Services for editorial assistance. This work was supported by the Chinese Medicine Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine (YN2016QJ03), the Guangdong Medical Science and Technology Research Foundation (A2018251), the China Postdoctoral Science Foundation's Sixty-third Batch of Projects (2018M630941), the doctoral research project of Guangdong Natural Science Foundation of China (2017A030310326), the Guangzhou Science and Technology Plan Project (201804010149), the Key Top-ranking Discipline Projects of Guangzhou University of Chinese Medicine (A1260619111001), the National Natural Science Foundation of China (81903991, 81974543), scholarships from the China Scholarship Council (201206380043 to SW) and Seoul National University Hospital (to DYO), and a grant from the National Cancer Institute (R01-CA90853 to FXC). The study was also supported by the NIH/NCI under award number P30CA016672 and used the Clinical Trials Support Resource and the Research Animal Support Facility. Funding Information: This work was supported by the Chinese Medicine Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine ( YN2016QJ03 ), the Guangdong Medical Science and Technology Research Foundation ( A2018251 ), the China Postdoctoral Science Foundation{\textquoteright}s Sixty-third Batch of Projects ( 2018M630941 ), the doctoral research project of Guangdong Natural Science Foundation of China ( 2017A030310326 ), the Guangzhou Science and Technology Plan Project ( 201804010149 ), the Key Top-ranking Discipline Projects of Guangzhou University of Chinese Medicine ( A1260619111001 ), the National Natural Science Foundation of China ( 81903991 , 81974543 ), scholarships from the China Scholarship Council ( 201206380043 to SW) and Seoul National University Hospital (to DYO), and a grant from the National Cancer Institute ( R01-CA90853 to FXC). The study was also supported by the NIH / NCI under award number P30CA016672 and used the Clinical Trials Support Resource and the Research Animal Support Facility. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = nov,
day = "28",
doi = "10.1016/j.canlet.2019.08.016",
language = "English (US)",
volume = "465",
pages = "12--23",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
}