Tumor Biology

, Volume 37, Issue 7, pp 8825–8839 | Cite as

MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells

  • Gillian Browne
  • Julie A. Dragon
  • Deli Hong
  • Terri L. Messier
  • Jonathan A. R. Gordon
  • Nicholas H. Farina
  • Joseph R. Boyd
  • Jennifer J. VanOudenhove
  • Andrew W. Perez
  • Sayyed K. Zaidi
  • Janet L. Stein
  • Gary S. Stein
  • Jane B. Lian
Original Article


The Runx1 transcription factor, known for its essential role in normal hematopoiesis, was reported in limited studies to be mutated or associated with human breast tumor tissues. Runx1 increases concomitantly with disease progression in the MMTV-PyMT transgenic mouse model of breast cancer. Compelling questions relate to mechanisms that regulate Runx1 expression in breast cancer. Here, we tested the hypothesis that dysregulation of Runx1-targeting microRNAs (miRNAs) allows for pathologic increase of Runx1 during breast cancer progression. Microarray profiling of the MMTV-PyMT model revealed significant downregulation of numerous miRNAs predicted to target Runx1. One of these, miR-378, was inversely correlated with Runx1 expression during breast cancer progression in mice and in human breast cancer cell lines MCF7 and triple-negative MDA-MB-231 that represent early- and late-stage diseases, respectively. MiR-378 is nearly absent in MDA-MB-231 cells. Luciferase reporter assays revealed that miR-378 binds the Runx1 3′ untranslated region (3′UTR) and inhibits Runx1 expression. Functionally, we demonstrated that ectopic expression of miR-378 in MDA-MB-231 cells inhibited Runx1 and suppressed migration and invasion, while inhibition of miR-378 in MCF7 cells increased Runx1 levels and cell migration. Depletion of Runx1 in late-stage breast cancer cells resulted in increased expression of both the miR-378 host gene PPARGC1B and pre-miR-378, suggesting a feedback loop. Taken together, our study identifies a novel and clinically relevant mechanism for regulation of Runx1 in breast cancer that is mediated by a PPARGC1B-miR-378-Runx1 regulatory pathway. Our results highlight the translational potential of miRNA replacement therapy for inhibiting Runx1 in breast cancer.


MiR-378 Runx1 Breast cancer MMTV-PyMT Invasion Migration 



This work was supported by the National Cancer Institute (Nos. P01 CA082834 and R03 CA167726), National Institute of Arthritis and Musculoskeletal and Skin Diseases (No. R01 AR039588), National Institute of Dental and Craniofacial Research (No. R37 DE012528), Pfizer (WS2049100), and grants from the University of Vermont Cancer Center and Lake Champlain Cancer Research Organization. The microarray research reported was supported by the National Institute of General Medical Sciences (No. P20 GM103449). The authors thank all members of our laboratories, especially Philip W. L. Tai, for valuable suggestions throughout the study. The authors are grateful to the UVM Cancer Center Advanced Genome Technologies Core, supported by UVM Cancer Center, Lake Champlain Cancer Research Organization, and the UVM College of Medicine for data pertaining to cell line authentication, as well as the Vermont Genetics Network Microarray Facility for miRNA target preparation, hybridization, and scanning processing. The authors are also grateful to the Molecular Bioinformatics Shared Resource of the University of Vermont College of Medicine for microarray data analysis. Finally, the authors thank the Advanced Genome Technologies Core Massively Parallel Sequencing Facility for sequencing data. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Compliance with ethical standards

Conflicts of interest


Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

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ESM 1 (PDF 1370 kb)
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  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Toss A, Cristofanilli M. Molecular characterization and targeted therapeutic approaches in breast cancer. Breast Cancer Res. 2015;17:60.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ichikawa M, Yoshimi A, Nakagawa M, Nishimoto N, Watanabe-Okochi N, Kurokawa M. A role for runx1 in hematopoiesis and myeloid leukemia. Int J Hematol. 2013;97:726–34.CrossRefPubMedGoogle Scholar
  5. 5.
    Scheitz CJ, Tumbar T. New insights into the role of runx1 in epithelial stem cell biology and pathology. J Cell Biochem. 2013;114:985–93.CrossRefPubMedGoogle Scholar
  6. 6.
    Hoi CS, Lee SE, Lu SY, McDermitt DJ, Osorio KM, Piskun CM, et al. Runx1 directly promotes proliferation of hair follicle stem cells and epithelial tumor formation in mouse skin. Mol Cell Biol. 2010;30:2518–36.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Heikinheimo K, Kurppa KJ, Laiho A, Peltonen S, Berdal A, Bouattour A, et al. Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor. J Dent Res. 2015;94:101–11.CrossRefPubMedGoogle Scholar
  8. 8.
    Keita M, Bachvarova M, Morin C, Plante M, Gregoire J, Renaud MC, et al. The runx1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion. Cell Cycle. 2013;12:972–86.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Wang X, Zhao Y, Qian H, Huang J, Cui F, Mao Z. The mir-101/runx1 feedback regulatory loop modulates chemo-sensitivity and invasion in human lung cancer. Int J Clin Exp Med. 2015;8:15030–42.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Jacques C, Guillotin D, Fontaine JF, Franc B, Mirebeau-Prunier D, Fleury A, et al. DNA microarray and miRNA analyses reinforce the classification of follicular thyroid tumors. J Clin Endocrinol Metab. 2013;98:E981–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.CrossRefGoogle Scholar
  12. 12.
    Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012;486:405–9.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012;486:353–60.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Chimge NO, Frenkel B. The runx family in breast cancer: relationships with estrogen signaling. Oncogene. 2013;32:2121–30.CrossRefPubMedGoogle Scholar
  15. 15.
    Ferrari N, Mohammed ZM, Nixon C, Mason SM, Mallon E, McMillan DC, et al. Expression of runx1 correlates with poor patient prognosis in triple negative breast cancer. PLoS One. 2014;9, e100759.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    van Bragt MP, Hu X, Xie Y, Li Z. Runx1, a transcription factor mutated in breast cancer, controls the fate of ER-positive mammary luminal cells. Elife. 2014;3, e03881.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Stender JD, Kim K, Charn TH, Komm B, Chang KC, Kraus WL, et al. Genome-wide analysis of estrogen receptor alpha DNA binding and tethering mechanisms identifies runx1 as a novel tethering factor in receptor-mediated transcriptional activation. Mol Cell Biol. 2010;30:3943–55.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Browne G, Taipaleenmaki H, Bishop NM, Madasu SC, Shaw LM, van Wijnen AJ, et al. Runx1 is associated with breast cancer progression in MMTV-PyMT transgenic mice and its depletion in vitro inhibits migration and invasion. J Cell Physiol. 2015;230:2522–32.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Tang W, Yu F, Yao H, Cui X, Jiao Y, Lin L, et al. Mir-27a regulates endothelial differentiation of breast cancer stem like cells. Oncogene. 2014;33:2629–38.CrossRefPubMedGoogle Scholar
  20. 20.
    Acunzo M, Romano G, Wernicke D, Croce CM. Microrna and cancer—a brief overview. Adv Biol Regul. 2015;57:1–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Browne G, Taipaleenmaki H, Stein GS, Stein JL, Lian JB. MicroRNAs in the control of metastatic bone disease. Trends Endocrinol Metab. 2014;25:320–7.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    van Schooneveld E, Wildiers H, Vergote I, Vermeulen PB, Dirix LY, Van Laere SJ. Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management. Breast Cancer Res. 2015;17:21.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Nana-Sinkam SP, Croce CM. MicroRNA regulation of tumorigenesis, cancer progression and interpatient heterogeneity: towards clinical use. Genome Biol. 2014;15:445.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Wilczynska A, Bushell M. The complexity of miRNA-mediated repression. Cell Death Differ. 2015;22:22–33.CrossRefPubMedGoogle Scholar
  26. 26.
    Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15:509–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769–73.CrossRefPubMedGoogle Scholar
  29. 29.
    Lujambio A, Lowe SW. The microcosmos of cancer. Nature. 2012;482:347–55.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Le Quesne J, Caldas C. Micro-RNAs and breast cancer. Mol Oncol. 2010;4:230–41.CrossRefPubMedGoogle Scholar
  31. 31.
    Berindan-Neagoe I, Monroig Pdel C, Pasculli B, Calin GA. MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA Cancer J Clin. 2014;64:311–36.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Iorio MV, Croce CM. Causes and consequences of microRNA dysregulation. Cancer J. 2012;18:215–22.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Arora S, Rana R, Chhabra A, Jaiswal A, Rani V. MiRNA-transcription factor interactions: a combinatorial regulation of gene expression. Mol Genet Genomics. 2013;288:77–87.CrossRefPubMedGoogle Scholar
  34. 34.
    Rossetti S, Sacchi N. Runx1: a microRNA hub in normal and malignant hematopoiesis. Int J Mol Sci. 2013;14:1566–88.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Taipaleenmaki H, Browne G, Akech J, Zustin J, van Wijnen AJ, Stein JL, et al. Targeting of runx2 by mir-135 and mir-203 impairs progression of breast cancer and metastatic bone disease. Cancer Res. 2015;75:1433–44.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Liu Z, Chen L, Zhang X, Xu X, Xing H, Zhang Y, et al. Runx3 regulates vimentin expression via mir-30a during epithelial-mesenchymal transition in gastric cancer cells. J Cell Mol Med. 2014;18:610–23.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lai KW, Koh KX, Loh M, Tada K, Subramaniam MM, Lim XY, et al. MicroRNA-130b regulates the tumour suppressor runx3 in gastric cancer. Eur J Cancer. 2010;46:1456–63.CrossRefPubMedGoogle Scholar
  38. 38.
    Wang M, Li C, Yu B, Su L, Li J, Ju J, et al. Overexpressed mir-301a promotes cell proliferation and invasion by targeting runx3 in gastric cancer. J Gastroenterol. 2013;48:1023–33.CrossRefPubMedGoogle Scholar
  39. 39.
    Lee DY, Deng Z, Wang CH, Yang BB. Microrna-378 promotes cell survival, tumor growth, and angiogenesis by targeting sufu and fus-1 expression. Proc Natl Acad Sci U S A. 2007;104:20350–5.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Ma J, Lin J, Qian J, Qian W, Yin J, Yang B, et al. Mir-378 promotes the migration of liver cancer cells by down-regulating fus expression. Cell Physiol Biochem. 2014;34:2266–74.CrossRefPubMedGoogle Scholar
  41. 41.
    Yu BL, Peng XH, Zhao FP, Liu X, Lu J, Wang L, et al. MicroRNA-378 functions as an onco-mir in nasopharyngeal carcinoma by repressing tob2 expression. Int J Oncol. 2014;44:1215–22.PubMedGoogle Scholar
  42. 42.
    Zhang GJ, Zhou H, Xiao HX, Li Y, Zhou T. Mir-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer. BMC Cancer. 2014;14:109.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Avgeris M, Stravodimos K, Scorilas A. Loss of mir-378 in prostate cancer, a common regulator of klk2 and klk4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients. Biol Chem. 2014;395:1095–104.CrossRefPubMedGoogle Scholar
  44. 44.
    Wang KY, Ma J, Zhang FX, Yu MJ, Xue JS, Zhao JS. MicroRNA-378 inhibits cell growth and enhances l-ohp-induced apoptosis in human colorectal cancer. IUBMB Life. 2014;66:645–54.CrossRefPubMedGoogle Scholar
  45. 45.
    Guy CT, Cardiff RD, Muller WJ. Induction of mammary tumors by expression of polyomavirus middle t oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol. 1992;12:954–61.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008;2008:pdb prot4986.Google Scholar
  47. 47.
    Romano P, Manniello A, Aresu O, Armento M, Cesaro M, Parodi B. Cell line data base: structure and recent improvements towards molecular authentication of human cell lines. Nucleic Acids Res. 2009;37:D925–32.CrossRefPubMedGoogle Scholar
  48. 48.
    Benjamini Y, Hochberg Y. Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc Ser B-Methodol. 1995;57:289–300.Google Scholar
  49. 49.
    Gutierrez S, Javed A, Tennant DK, van Rees M, Montecino M, Stein GS, et al. Ccaat/enhancer-binding proteins (c/ebp) beta and delta activate osteocalcin gene transcription and synergize with runx2 at the c/ebp element to regulate bone-specific expression. J Biol Chem. 2002;277:1316–23.CrossRefPubMedGoogle Scholar
  50. 50.
    Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase ii in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983;11:1475–89.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.CrossRefPubMedGoogle Scholar
  52. 52.
    Feng J, Liu T, Qin B, Zhang Y, Liu XS. Identifying CHiP-seq enrichment using MACS. Nat Protoc. 2012;7:1728–40.CrossRefPubMedGoogle Scholar
  53. 53.
    Lin EY, Jones JG, Li P, Zhu L, Whitney KD, Muller WJ, et al. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am J Pathol. 2003;163:2113–26.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Chavez KJ, Garimella SV, Lipkowitz S. Triple negative breast cancer cell lines: one tool in the search for better treatment of triple negative breast cancer. Breast Dis. 2010;32:35–48.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res. 2011;13:215.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Kimura H. Histone modifications for human epigenome analysis. J Hum Genet. 2013;58:439–45.CrossRefPubMedGoogle Scholar
  57. 57.
    Benayoun BA, Pollina EA, Ucar D, Mahmoudi S, Karra K, Wong ED, et al. H3k4me3 breadth is linked to cell identity and transcriptional consistency. Cell. 2014;158:673–88.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Eichner LJ, Perry MC, Dufour CR, Bertos N, Park M, St-Pierre J, et al. Mir-378(*) mediates metabolic shift in breast cancer cells via the pgc-1beta/errgamma transcriptional pathway. Cell Metab. 2010;12:352–61.CrossRefPubMedGoogle Scholar
  59. 59.
    Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.PubMedGoogle Scholar
  60. 60.
    Bowers SR, Calero-Nieto FJ, Valeaux S, Fernandez-Fuentes N, Cockerill PN. Runx1 binds as a dimeric complex to overlapping runx1 sites within a palindromic element in the human GM-CSF enhancer. Nucleic Acids Res. 2010;38:6124–34.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Speck NA, Terryl S. A new transcription factor family associated with human leukemias. Crit Rev Eukaryot Gene Expr. 1995;5:337–64.CrossRefPubMedGoogle Scholar
  62. 62.
    Serpico D, Molino L, Di Cosimo S. MicroRNAs in breast cancer development and treatment. Cancer Treat Rev. 2014;40:595–604.CrossRefPubMedGoogle Scholar
  63. 63.
    Hassan MQ, Maeda Y, Taipaleenmaki H, Zhang W, Jafferji M, Gordon JA, et al. Mir-218 directs a Wnt signaling circuit to promote differentiation of osteoblasts and osteomimicry of metastatic cancer cells. J Biol Chem. 2012;287:42084–92.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Hassan MQ, Gordon JA, Beloti MM, Croce CM, van Wijnen AJ, Stein JL, et al. A network connecting runx2, satb2, and the mir-23a∼27a∼24-2 cluster regulates the osteoblast differentiation program. Proc Natl Acad Sci U S A. 2010;107:19879–84.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Ben-Ami O, Pencovich N, Lotem J, Levanon D, Groner Y. A regulatory interplay between mir-27a and runx1 during megakaryopoiesis. Proc Natl Acad Sci U S A. 2009;106:238–43.CrossRefPubMedGoogle Scholar
  66. 66.
    Zaidi SK, Dowdy CR, van Wijnen AJ, Lian JB, Raza A, Stein JL, et al. Altered runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a mir-24/MKP-7/MAPK network. Cancer Res. 2009;69:8249–55.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Yin JY, Deng ZQ, Liu FQ, Qian J, Lin J, Tang Q, et al. Association between mir-24 and mir-378 in formalin-fixed paraffin-embedded tissues of breast cancer. Int J Clin Exp Pathol. 2014;7:4261–7.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Knezevic I, Patel A, Sundaresan NR, Gupta MP, Solaro RJ, Nagalingam RS, et al. A novel cardiomyocyte-enriched microRNA, mir-378, targets insulin-like growth factor 1 receptor: implications in postnatal cardiac remodeling and cell survival. J Biol Chem. 2012;287:12913–26.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Christopoulos PF, Msaouel P, Koutsilieris M. The role of the insulin-like growth factor-1 system in breast cancer. Mol Cancer. 2015;14:43.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Pande S, Browne G, Padmanabhan S, Zaidi SK, Lian JB, van Wijnen AJ, et al. Oncogenic cooperation between pi3k/akt signaling and transcription factor runx2 promotes the invasive properties of metastatic breast cancer cells. J Cell Physiol. 2013;228:1784–92.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Chang YY, Kuo WH, Hung JH, Lee CY, Lee YH, Chang YC, et al. Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing. Mol Cancer. 2015;14:36.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Jiang L, Huang Q, Zhang S, Zhang Q, Chang J, Qiu X, et al. Hsa-mir-125a-3p and hsa-mir-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells. BMC Cancer. 2010;10:318.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Guo L, Lu Z. The fate of miRNA* strand through evolutionary analysis: implication for degradation as merely carrier strand or potential regulatory molecule? PLoS One. 2010;5, e11387.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, et al. Gata-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell. 2008;13:141–52.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013;12:847–65.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Bouchie A. First microRNA mimic enters clinic. Nat Biotechnol. 2013;31:577.CrossRefPubMedGoogle Scholar
  77. 77.
    Bader AG. Mir-34—a microRNA replacement therapy is headed to the clinic. Front Genet. 2012;3:120.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Gillian Browne
    • 1
  • Julie A. Dragon
    • 2
  • Deli Hong
    • 1
  • Terri L. Messier
    • 1
  • Jonathan A. R. Gordon
    • 1
  • Nicholas H. Farina
    • 1
  • Joseph R. Boyd
    • 1
  • Jennifer J. VanOudenhove
    • 1
  • Andrew W. Perez
    • 1
  • Sayyed K. Zaidi
    • 1
  • Janet L. Stein
    • 1
  • Gary S. Stein
    • 1
  • Jane B. Lian
    • 1
  1. 1.Department of Biochemistry & University of Vermont Cancer CenterUniversity of Vermont College of MedicineBurlingtonUSA
  2. 2.Department of Microbiology and Molecular GeneticsUniversity of VermontBurlingtonUSA

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