MicroRNA-4417 is a tumor suppressor and prognostic biomarker for triple-negative breast cancer

被引:21
|
作者
Wong, Chen Khuan [1 ,2 ]
Gromisch, Christopher [3 ]
Ozturk, Sait [4 ,5 ]
Papageorgis, Panagiotis [6 ]
Abdolmaleky, Hamid Mostafavi [2 ]
Reinhard, Bjoern M. [7 ]
Thiagalingam, Arunthathi [2 ,8 ]
Thiagalingam, Sam [1 ,2 ,3 ,4 ,9 ]
机构
[1] Boston Univ, Sch Med, Grad Program Genet & Genom, 72 East Concord St, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Med, Biomed Genet Sect, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA
[4] Boston Univ, Sch Med, Grad Program Mol & Translat Med, Boston, MA 02118 USA
[5] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Oncol Sci, New York, NY 10029 USA
[6] European Univ Cyprus, Sch Sci, Dept Life Sci, Nicosia, Cyprus
[7] Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA
[8] IPSEN Biosci Inc, Translat Sci, Cambridge, MA USA
[9] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA
关键词
Triple-negative breast cancer; tumor suppressor; miRNA; epithelial-mesencyhmal transition; EPITHELIAL-MESENCHYMAL TRANSITION; MIR-200; FAMILY; BASAL-LIKE; SURVIVAL; METASTASIS; EXPRESSION; CELLS; INHIBITION; PHENOTYPE; KINASE;
D O I
10.1080/15384047.2019.1595285
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor prognosis due to lack of druggable targets such as hormone and growth factor receptors. Therefore, identification of targetable regulators such as miRNAs could provide new avenues for therapeutic applications. Here, we report that the expression of miR-4417 is suppressed during the progression of TNBC cells from non-malignant to the malignant stage. MiR-4417 is localized to chromosome 1p36, a region with high frequency of loss of heterozygosity in multiple cancers, and its biogenesis is DICER-dependent. Low expression of miR-4417 is significantly associated with worse prognosis in TNBC patients, while overexpression of miR-4417 is sufficient to inhibit migration and mammosphere formation of TNBC cells in vitro. Overall, our findings suggest miR-4417 exerts a tumor suppressive effect and thereby could serve as a prognostic biomarker and therapeutic tool against TNBC.
引用
收藏
页码:1113 / 1120
页数:8
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