title: 14q32-encoded microRNAs mediate an oligometastatic phenotype.
abstract: Oligometastasis is a clinically distinct subset of metastasis characterized by a limited number of metastases potentially curable with localized therapies. We analyzed pathways targeted by microRNAs over-expressed in clinical oligometastasis samples and identified suppression of cellular adhesion, invasion, and motility pathways in association with the oligometastatic phenotype. We identified miR-127-5p, miR-544a, and miR-655-3p encoded in the 14q32 microRNA cluster as co-regulators of multiple metastatic pathways through repression of shared target genes. These microRNAs suppressed cellular adhesion and invasion and inhibited metastasis development in an animal model of breast cancer lung colonization. Target genes, including TGFBR2 and ROCK2, were key mediators of these effects. Understanding the role of microRNAs expressed in oligometastases may lead to improved identification of and interventions for patients with curable metastatic disease, as well as an improved understanding of the molecular basis of this unique clinical entity.
authors: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors: Abhineet
authors: A
authors: Uppal
authors: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors: Sean C
authors: SC
authors: Wightman
authors: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Stephen
authors: S
authors: Mallon
authors: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors: Go
authors: G
authors: Oshima
authors: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Sean P
authors: SP
authors: Pitroda
authors: Department of Pathology, Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA.
authors: Qingbei
authors: Q
authors: Zhang
authors: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Xiaona
authors: X
authors: Huang
authors: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Thomas E
authors: TE
authors: Darga
authors: Center for Research Informatics, The University of Chicago, Chicago, IL 60637, USA.
authors: Lei
authors: L
authors: Huang
authors: Center for Research Informatics, The University of Chicago, Chicago, IL 60637, USA.
authors: Jorge
authors: J
authors: Andrade
authors: Department of Pathology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Huiping
authors: H
authors: Liu
authors: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Mark K
authors: MK
authors: Ferguson
authors: Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.|The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Geoffrey L
authors: GL
authors: Greene
authors: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Mitchell C
authors: MC
authors: Posner
authors: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Samuel
authors: S
authors: Hellman
authors: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Nikolai N
authors: NN
authors: Khodarev
authors: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.|Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Ralph R
authors: RR
authors: Weichselbaum
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002883:Chromosomes, Human, Pair 14; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype
chemical_list: D035683:MicroRNAs