miR-20b is up-regulated in brain metastases from primary breast cancers

被引:50
作者
Ahmad, Aamir [1 ,2 ]
Ginnebaugh, Kevin R. [1 ,2 ]
Sethi, Seema [1 ,2 ]
Chen, Wei [2 ,3 ]
Ali, Rouba [2 ,3 ]
Mittal, Sandeep [2 ,3 ,4 ]
Sarkar, Fazlul H. [1 ,2 ,3 ]
机构
[1] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA
[2] Karmanos Canc Inst, Detroit, MI USA
[3] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA
[4] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA
关键词
miR-20b; breast cancer; brain metastasis; EXPRESSION; MICRORNAS; CELLS; STATISTICS; SURVIVAL; GROWTH;
D O I
10.18632/oncotarget.3664
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with > 50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.
引用
收藏
页码:12188 / 12195
页数:8
相关论文
共 35 条
[1]
Ahmad A, 2014, AM J TRANSL RES, V6, P384
[2]
Spectrum of breast cancer metastasis in BRCA1 mutation carriers:: highly increased incidence of brain metastases [J].
Albiges, L ;
André, F ;
Balleyguier, C ;
Gomez-Abuin, G ;
Chompret, A ;
Delaloge, S .
ANNALS OF ONCOLOGY, 2005, 16 (11) :1846-U3
[3]
[Anonymous], BREAST CANC METASTAS
[4]
[Anonymous], OA MOL ONCOLOGY
[5]
Complete Loss of PTEN Protein Expression Correlates with Shorter Time to Brain Metastasis and Survival in Stage IIIB/C Melanoma Patients with BRAFV600 Mutations [J].
Bucheit, Amanda D. ;
Chen, Guo ;
Siroy, Alan ;
Tetzlaff, Michael ;
Broaddus, Russell ;
Milton, Denai ;
Fox, Patricia ;
Bassett, Roland ;
Hwu, Patrick ;
Gershenwald, Jeffrey E. ;
Lazar, Alexander J. ;
Davies, Michael A. .
CLINICAL CANCER RESEARCH, 2014, 20 (21) :5527-5536
[6]
miR-20b Modulates VEGF Expression by Targeting HIF-1α and STAT3 in MCF-7 Breast Cancer Cells [J].
Cascio, Sandra ;
D'Andrea, Aleco ;
Ferla, Rita ;
Surmacz, Eva ;
Gulotta, Eliana ;
Amodeo, Valeria ;
Bazan, Viviana ;
Gebbi, Nicola ;
Russo, Antonio .
JOURNAL OF CELLULAR PHYSIOLOGY, 2010, 224 (01) :242-249
[7]
The estrogen receptor-α-induced microRNA signature regulates itself and its transcriptional response [J].
Castellano, Leandro ;
Giamas, Georgios ;
Jacob, Jimmy ;
Coombes, R. Charles ;
Lucchesi, Walter ;
Thiruchelvam, Paul ;
Barton, Geraint ;
Jiao, Long R. ;
Wait, Robin ;
Waxman, Jonathan ;
Hannon, Gregory J. ;
Stebbing, Justin .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (37) :15732-15737
[8]
Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm [J].
Cheung, Tak-hong ;
Man, Kwun-nok Mimi ;
Yu, Mei-yung ;
Yim, So-fan ;
Siu, Nelson S. S. ;
Lo, Keith W. K. ;
Doran, Graeme ;
Wong, Raymond R. Y. ;
Wang, Vivian W. ;
Smith, David I. ;
Worley, Michael J., Jr. ;
Berkowitz, Ross S. ;
Chung, Tony K. H. ;
Wong, Yick-fu .
CELL CYCLE, 2012, 11 (15) :2876-2884
[9]
Cancer Treatment and Survivorship Statistics, 2014 [J].
DeSantis, Carol E. ;
Lin, Chun Chieh ;
Mariotto, Angela B. ;
Siegel, Rebecca L. ;
Stein, Kevin D. ;
Kramer, Joan L. ;
Alteri, Rick ;
Robbins, Anthony S. ;
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2014, 64 (04) :252-271
[10]
Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients [J].
Duchnowska, Renata ;
Jassem, Jacek ;
Goswami, Chirayu Pankaj ;
Dundar, Murat ;
Goekmen-Polar, Yesim ;
Li, Lang ;
Woditschka, Stephan ;
Biernat, Wojciech ;
Sosinska-Mielcarek, Katarzyna ;
Czartoryska-Arlukowicz, Bogumila ;
Radecka, Barbara ;
Tomasevic, Zorica ;
Stepniak, Piotr ;
Wojdan, Konrad ;
Sledge, George W., Jr. ;
Steeg, Patricia S. ;
Badve, Sunil .
JOURNAL OF NEURO-ONCOLOGY, 2015, 122 (01) :205-216