title: miR-20b is up-regulated in brain metastases from primary breast cancers.
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.
authors.affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Ginnebaugh
authors.affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali
authors.affiliation: Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.|Department of Neurosurgery, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.|Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D011379:Prognosis; D012307:Risk Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs
keywords: brain metastasis; breast cancer; miR-20b