title: Transcriptional changes induced by the tumor dormancy-associated microRNA-190.
abstract: Tumor dormancy is a highly prevalent stage in cancer progression. We have previously generated and characterized in vivo experimental models of human tumor dormancy in which micro-tumors remain occult until they spontaneously shift into rapid tumor growth. We showed that the dormant micro-tumors undergo a stable microRNA (miRNA) switch during their transition from dormancy to a fast-growing phenotype and reported the identification of a consensus signature of human tumor dormancy-associated miRNAs (DmiRs). miRNA-190 (miR-190) is among the most upregulated DmiRs in all dormant tumors analyzed. Upregulation of miR-190 led to prolonged tumor dormancy in otherwise fast-growing glioblastomas and osteosarcomas. Here we investigate the transcriptional changes induced by miR-190 expression in cancer cells and show similar patterns of miR-190 mediated transcriptional reprogramming in both glioblastoma and osteosarcoma cells. The data suggests that miR-190 mediated effects rely on an extensive network of molecular changes in tumor cells and that miR-190 affects several transcriptional factors, tumor suppressor genes and interferon response pathways. The molecular mechanisms governing tumor dormancy described in this work may provide promising targets for early prevention of cancer and may lead to novel treatments to convert the malignant tumor phenotype into an asymptomatic dormant state.
authors.affiliation: Center of Cancer Systems Biology; Tufts University School of Medicine; Boston, MA.
authors.forename: Nava
authors.initials: N
authors.lastname: Almog
authors.forename: Christine
authors.initials: C
authors.lastname: Briggs
authors.forename: Afshin
authors.initials: A
authors.lastname: Beheshti
authors.forename: Lili
authors.initials: L
authors.lastname: Ma
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: Wilkie
authors.forename: Edward
authors.initials: E
authors.lastname: Rietman
authors.forename: Lynn
authors.initials: L
authors.lastname: Hlatky
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D049029:Dystrophin-Associated Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D049029:Dystrophin-Associated Proteins; C576613:MIRN190 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C091824:syntrophin; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl
keywords: glioblastoma; microRNA; osteosarcoma; transcriptional reprogramming; tumor dormancy