Oncotarget

Research Papers:

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

Aamir Ahmad, Kevin R. Ginnebaugh, Seema Sethi, Wei Chen, Rouba Ali, Sandeep Mittal and Fazlul H. Sarkar _

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Oncotarget. 2015; 6:12188-12195. https://doi.org/10.18632/oncotarget.3664

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Abstract

Aamir Ahmad1, Kevin R. Ginnebaugh1, Seema Sethi1, Wei Chen2, Rouba Ali2, Sandeep Mittal2,3 and Fazlul H. Sarkar1,2

1 Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA

2 Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA

3 Department of Neurosurgery, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA

Correspondence to:

Fazlul H. Sarkar, email:

Keywords: miR-20b, breast cancer, brain metastasis

Received: January 27, 2015 Accepted: March 02, 2015 Published: March 26, 2015

Abstract

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.


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