Abstract
Brian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.
Highlights
Brain metastases are the most common brain malignancy that frequently arises from 15 to 25% advanced breast cancer (BC) patients [1, 2]
To identify the novel miRNAs involved in brain-specific metastasis in triple-negative breast cancer (TNBC), brain-tropic BC cell lines (BrM1, BrM2, and BrM3) derived from MDA-MB-231 were established through a series of in vivo selections (Supplementary Fig. S1A, as described in Supplementary information)
Brain metastasis of mice injected with BrM2 and BrM3 cells could be detected 3–7 days after injection, whereas the parental cell signal was undetectable till the third week after injection (Fig. 1C)
Summary
Brain metastases are the most common brain malignancy that frequently arises from 15 to 25% advanced breast cancer (BC) patients [1, 2]. University Hospital, Tainan, Taiwan with brain metastasis is due to limiting therapeutic strategies and lack of prognostic biomarkers. Identification and characterization of the brain metastasis prognostic biomarker is the critical issue for patients’ treatment. Cancer cells interacted with the BBB structure play a critical role in brain metastasis and tumor relapse. To predict brain metastasis in TNBC patients. Upregulation of miR-141 promotes the mesenchymal to epithelial transition in brain-tropic TNBC cells [24]. We established available experimental in vitro and in vivo models of TNBC brain metastasis to investigate and characterize the functional role of miR-211 in TNBC brain metastasis. Plasma high miR-211 was demonstrated to predict TNBC brain metastasis in vivo
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