title: miR-141-Mediated Regulation of Brain Metastasis From Breast Cancer.
abstract: Brain metastasis poses a major treatment challenge and remains an unmet clinical need. Finding novel therapies to prevent and treat brain metastases requires an understanding of the biology and molecular basis of the process, which currently is constrained by a dearth of experimental models and specific therapeutic targets.
  
  
  
  Green Fluorescent Protein (GFP)-labeled breast cancer cells were injected via tail vein into SCID/Beige mice (n = 10-15 per group), and metastatic colonization to the brain and lung was evaluated eight weeks later. Knockdown and overexpression of miR-141 were achieved with lentiviral vectors. Serum levels of miR-141 were measured from breast cancer patients (n = 105), and the association with clinical outcome was determined by Kaplan-Meier method. All statistical tests were two-sided.
  
  
  
  Novel brain metastasis mouse models were developed via tail vein injection of parental triple-negative and human epidermal growth factor receptor 2 (HER2)-overexpressing inflammatory breast cancer lines. Knockdown of miR-141 inhibited metastatic colonization to brain (miR-141 knockdown vs control: SUM149, 0/8 mice vs 6/9 mice,P= .009; MDA-IBC3, 2/14 mice vs 10/15 mice,P= .007). Ectopic expression of miR-141 in nonexpressing MDA-MB-231 enhanced brain metastatic colonization (5/9 mice vs 0/10 mice,P= .02). Furthermore, high miR-141 serum levels were associated with shorter brain metastasis-free survival (P= .04) and were an independent predictor of progression-free survival (hazard ratio [HR] = 4.77, 95% confidence interval [CI] = 2.61 to 8.71,P< .001) and overall survival (HR = 7.22, 95% CI = 3.46 to 15.06,P< .001).
  
  
  
  Our study suggests miR-141 is a regulator of brain metastasis from breast cancer and should be examined as a biomarker and potential target to prevent and treat brain metastases.
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Bisrat G
authors.initials: BG
authors.lastname: Debeb
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Lara
authors.initials: L
authors.lastname: Lacerda
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Simone
authors.initials: S
authors.lastname: Anfossi
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Parmeswaran
authors.initials: P
authors.lastname: Diagaradjane
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Khoi
authors.initials: K
authors.lastname: Chu
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Arvind
authors.initials: A
authors.lastname: Bambhroliya
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Lei
authors.initials: L
authors.lastname: Huo
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Caimiao
authors.initials: C
authors.lastname: Wei
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Adam R
authors.initials: AR
authors.lastname: Wolfe
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Allen
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wu
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Xiang H
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
authors.affiliation: Affiliation of authors: Departments of Experimental Radiation Oncology (BGD, LLa, PD, RAL, ARW, WX, DLS, LLi), Hematopathology (SA, JMR), Experimental Therapeutics (KC, CI, GAC), Pathology (LH, SK), Biostatistics (CW, WW), Radiation Oncology (AB, PKA, TAB, WAW), and Breast Medical Oncology (NTU), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX (XHZ); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX (BGD, LLa, SA, LH, RAL, ARW, WX, DLS, LLi, SK, TAB, NTU, JMR, WAW).
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000097:blood / Q000235:genetics* / Q000556:secondary*; D015820:Cadherins / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000235:genetics* / Q000556:secondary; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D064726:Triple Negative Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*
chemical_list: D015820:Cadherins; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; C533895:MIRN141 microRNA, human; C508053:ERBB2 protein, human