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.
Highlights
Breast cancer is one of the most commonly diagnosed solid malignancies and the leading cause of cancer-related deaths among women
There is evidence to suggest that miR-20b is involved in regulation of estrogen receptor (ER) [17], so, we chose ER-positive MCF-7 cells as our model to investigate in vitro effects of miR-20b modulation
For the patients with brain metastasis, we evaluated the levels of miR-20b in the primary breast tumor as well as the brain metastasis of the same patient. miR-20b levels were significantly higher in the brain tumor samples of the patients with brain metastases, compared to the samples from patients without brain www.impactjournals.com/oncotarget metastases (Figure 3)
Summary
Breast cancer is one of the most commonly diagnosed solid malignancies and the leading cause of cancer-related deaths among women. In 2015, breast cancer alone is expected to account for 29% of all new cancers among women in the United States [1]. Medical advancements in recent years, combined with aggressive screening programs, have significantly reduced breast cancer-related mortality, but the numbers are still too high. Among millions of Americans with a history of cancer, breast cancer tops the list of most prevalent cancers among women with 41% [2]. Breast cancer is a complex disease with many subtypes and one primary reason that makes breast cancer lethal is its metastasis to distant organs. Breast cancer is the second leading cause of brain metastases and significantly impacts patient’s quality of life [3]
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