MiRNA-20a-5p promotes the growth of triple-negative breast cancer cells through targeting RUNX3

被引:83
作者
Bai, Xiangdong [1 ,3 ]
Han, Guohui [3 ]
Liu, Yang [3 ]
Jiang, Hongchuan [2 ]
He, Qiang [1 ]
机构
[1] Capital Med Univ, Beijing Chaoyang Hosp, Dept Hepatobiliary Surg, Affiliated Hosp, Beijing, Peoples R China
[2] Capital Med Univ, Beijing Chaoyang Hosp, Dept Breast Surg, Affiliated Hosp, Beijing, Peoples R China
[3] Shanxi Med Univ, Shanxi Prov Canc Hosp, Dept Breast Surg, Taiyuan, Shanxi, Peoples R China
关键词
miR-20a-5p; Triple-negative breast cancer; RUNX3; Cell proliferation; MIR-20A; METASTASIS; INVASION; EXPRESSION; AUTOPHAGY;
D O I
10.1016/j.biopha.2018.04.165
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Increasing evidence showed that microRNAs (miRNAs) were abnormally expressed in cancers and made effects on the tumorigenesis. Aberrant expression of miR-20a-5p has been reported in human breast carcinoma. However, the functional mechanism of miR-20a-5p in human breast carcinoma, particularly in triple-negative breast cancer (TNBC), required further investigations. Here, firstly, we determined that miR-20a-5p was highly expressed in both TNBC tissues and cell lines. Then, we explored that the overexpression of miR-20a-5p promoted the migration and invasion of TNBC cells in vitro. The tendency was significantly reversed after the depletion of miR-20a-5p. Consistent result could be obtained with the in vivo nude mice tumorigenesis. Thirdly, the underlying molecular mechanism was investigated. The Runt-related transcription factor 3 (RUNX3) was identified as a target of miR-20a-5p in TNBC cells. High expression of miR-20a-5p significantly decreased both the mRNA and protein levels of RUNX3, as well as its direct downstream targets Bim and p21. These results verified the significance of miR-20a-5p and explored its functional mechanisms in TNBC, suggesting the potential clinical applications of miR-20a-5p in TNBC.
引用
收藏
页码:1482 / 1489
页数:8
相关论文
共 30 条
[1]   miR-20b is up-regulated in brain metastases from primary breast cancers [J].
Ahmad, Aamir ;
Ginnebaugh, Kevin R. ;
Sethi, Seema ;
Chen, Wei ;
Ali, Rouba ;
Mittal, Sandeep ;
Sarkar, Fazlul H. .
ONCOTARGET, 2015, 6 (14) :12188-12195
[2]   Integrated MicroRNA-mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer [J].
Bottai, Giulia ;
Diao, Lixia ;
Baggerly, Keith A. ;
Paladini, Laura ;
Gyorffy, Balzs ;
Raschioni, Carlotta ;
Pusztai, Lajos ;
Calin, George A. ;
Santarpia, Libero .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (01)
[3]   Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p [J].
Cabral Calvano Filho, Carlos Marino ;
Calvano-Mendes, Daniele Carvalho ;
Carvalho, Katia Candido ;
Maciel, Gustavo Arantes ;
Ricci, Marcos Desiderio ;
Torres, Ana Paula ;
Filassi, Jose Roberto ;
Baracat, Edmund Chada .
TUMOR BIOLOGY, 2014, 35 (08) :7733-7741
[4]   The emerging role of RUNX3 in cancer metastasis [J].
Chen, Feifei ;
Liu, Xin ;
Bai, Jin ;
Pei, Dongsheng ;
Zheng, Junnian .
ONCOLOGY REPORTS, 2016, 35 (03) :1227-1236
[5]   MicroRNA-20a-5p targets RUNX3 to regulate proliferation and migration of human hepatocellular cancer cells [J].
Chen, Yanke ;
Wang, Xiaofei ;
Cheng, Jiwen ;
Wang, Zhen ;
Jiang, Ting ;
Hou, Ni ;
Liu, Na ;
Song, Tusheng ;
Huang, Chen .
ONCOLOGY REPORTS, 2016, 36 (06) :3379-3386
[6]   The lncRNA HOTAIRM1 regulates the degradation of PML-RARA oncoprotein and myeloid cell differentiation by enhancing the autophagy pathway [J].
Chen, Zhen-Hua ;
Wang, Wen-Tao ;
Huang, Wei ;
Fang, Ke ;
Sun, Yu-Meng ;
Liu, Shu-Rong ;
Luo, Xue-Qun ;
Chen, Yue-Qin .
CELL DEATH AND DIFFERENTIATION, 2017, 24 (02) :212-224
[7]   MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4 [J].
Cheng, Dantong ;
Zhao, Senlin ;
Tang, Huamei ;
Zhang, Dongyuan ;
Sun, Hongcheng ;
Yu, Fudong ;
Jiang, Weiliang ;
Yue, Ben ;
Wang, Jingtao ;
Zhang, Meng ;
Yu, Yang ;
Liu, Xisheng ;
Sun, Xiaofeng ;
Zhou, Zongguang ;
Qin, Xuebin ;
Zhang, Xin ;
Yan, Dongwang ;
Wen, Yugang ;
Peng, Zhihai .
ONCOTARGET, 2016, 7 (29) :45199-45213
[8]   MMTV-PyMT and Derived Met-1 Mouse Mammary Tumor Cells as Models for Studying the Role of the Androgen Receptor in Triple-Negative Breast Cancer Progression [J].
Christenson, Jessica L. ;
Butterfield, Kiel T. ;
Spoelstra, Nicole S. ;
Norris, John D. ;
Josan, Jatinder S. ;
Pollock, Julie A. ;
McDonnell, Donald P. ;
Katzenellenbogen, Benita S. ;
Katzenellenbogen, John A. ;
Richer, Jennifer K. .
HORMONES & CANCER, 2017, 8 (02) :69-77
[9]   Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4 [J].
Cittelly, D. M. ;
Finlay-Schultz, J. ;
Howe, E. N. ;
Spoelstra, N. S. ;
Axlund, S. D. ;
Hendricks, P. ;
Jacobsen, B. M. ;
Sartorius, C. A. ;
Richer, J. K. .
ONCOGENE, 2013, 32 (20) :2555-2564
[10]   Triple-Negative Breast Cancer: An Unmet Medical Need [J].
Hudis, Clifford A. ;
Gianni, Luca .
ONCOLOGIST, 2011, 16 :1-11