Cancer Lett. 2019;465:12-23.
MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer.
제1저자 Sumei Wang, 오도연 · 교신저자 Sumei Wang, Wanyin Wu, Francois Claret.
소속 (8)
- Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, PR China; The Postdoctoral Research Station, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong Province, PR China; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: wangsumei198708@163.com.
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
- Department of Pathology, Medical College of Wisconsin Milwaukee, Wisconsin, USA.
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong Province, PR China. Electronic address: wwanyin@126.com.
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Experimental Therapeutics, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA; Cancer Biology Programs, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address: fxclaret@mdanderson.org.
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.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
Keywords
JAB1/CSN5Therapeutic targetTriple-negative breast cancermicroRNA
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- 저널
- Cancer letters · eISSN 1872-7980
- 전자 출판
- 2019-08-29
- MeSH
- Animals · COP9 Signalosome Complex / genetics / metabolism · Cell Line, Tumor · Cell Proliferation · Cisplatin / administration & dosage / pharmacology · Drug Resistance, Neoplasm* · Female · Gene Expression Regulation, Neoplastic · Humans · Intracellular Signaling Peptides and Proteins / genetics / metabolism · Mice · MicroRNAs / genetics · Middle Aged · Peptide Hydrolases / genetics / metabolism · Prognosis · Triple Negative Breast Neoplasms / genetics / metabolism / pathology · Up-Regulation · Xenograft Model Antitumor Assays
- Substances
- Intracellular Signaling Peptides and Proteins · MIRN17 microRNA, human · MicroRNAs · Peptide Hydrolases · COPS5 protein, human · COP9 Signalosome Complex · Cisplatin
- 연구비
- NCI NIH HHS R01 CA090853 · NCI NIH HHS P30 CA016672