期刊
CANCER LETTERS
卷 465, 期 -, 页码 12-23出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.08.016
关键词
Triple-negative breast cancer; microRNA; JAB1/CSN5; Therapeutic target
类别
资金
- Chinese Medicine Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine [YN2016QJ03]
- Guangdong Medical Science and Technology Research Foundation [A2018251]
- China Postdoctoral Science Foundation's Sixty-third Batch of Projects [2018M630941]
- Guangdong Natural Science Foundation of China [2017A030310326]
- Guangzhou Science and Technology Plan Project [201804010149]
- Key Top-ranking Discipline Projects of Guangzhou University of Chinese Medicine [A1260619111001]
- National Natural Science Foundation of China [81903991, 81974543]
- China Scholarship Council [201206380043]
- Seoul National University Hospital
- National Cancer Institute [R01-CA90853]
- NIH/NCI [P30CA016672]
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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