4.4 Article

MicroRNA-199a-3p promotes drug sensitivity in triple negative breast cancer by down-regulation of BRCA1

期刊

AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
卷 14, 期 3, 页码 2021-2036

出版社

E-CENTURY PUBLISHING CORP

关键词

MicroRNA; BRCA1; triple negative breast cancer; chemoresistance

资金

  1. Dr. Ellen Li Charitable Foundation
  2. Kerry Kuok Foundation
  3. Hong Kong Hereditary Breast Cancer Family Registry
  4. Health and Medical Research Fund [03143406]
  5. Asian Fund for Cancer Research and Seed Funding for Basic Research [201511159129]

向作者/读者索取更多资源

In this study, the researchers investigated the effects of miR-199a-3p-mediated BRCA1 dysfunction on triple negative breast cancer (TNBC) progression and chemosensitivity. They found that miR-199a-3p directly targeted BRCA1 in TNBC cells, leading to its downregulation and inhibiting tumor growth. Moreover, miR-199a-3p reversed cisplatin resistance and sensitized TNBC cells to veliparib, potentially by repressing DNA repair ability and inducing cell apoptosis.
MiR-199a-3p was previously predicted to target tumor suppressor gene BRCA1, which has been linked to cancer onset and therapeutic response. In this study, the effects of miR-199a-3p-mediated BRCA1 dysfunction on triple negative breast cancer (TNBC) progression and chemosensitivity were assessed. The association between miR-199a-3p and BRCA1 expression was examined in TNBC tumors and verified with luciferase reporter and protein assays. Tumorigenic functions of miR-199a-3p in TNBC cells were investigated by cell proliferation, clonogenic and migration assays. The sensitivities to chemotherapeutic drugs were tested with cisplatin and PARP inhibitor (veliparib) treatments. Mouse xenograft model was used to examine the effects of miR-199a-3p on tumor growth and drug response in vivo. MiR-199a-3p was shown to directly target BRCA1 in TNBC cells, resulting its downregulation and reduced luciferase reporter activity mediated by BRCA1 3'-UTR. Ectopic miR-199a-3p in TNBC cells exerted inhibitory effects on cell proliferation, migration and xenograft tumor growth. Moreover, miR-199a-3p was shown to reverse cisplatin-resistance and sensitize TNBC cells to veliparib, which might be due to repressed DNA repair ability and induced cell apoptosis. Our results demonstrated the tumor suppressive effects of miR-199a-3p on TNBC and induction on chemotherapeutic sensitivities, which were correlated with BRCA1 gene dysfunction. These findings may provide insights into the potential prognostic and therapeutic values of miR-199a-3p in patients with TNBC.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据