Transcriptional changes induced by the tumor dormancy-associated microRNA-190

Transcription. Jul-Aug 2013;4(4):177-91. doi: 10.4161/trns.25558. Epub 2013 Jul 1.

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.

Keywords: glioblastoma; microRNA; osteosarcoma; transcriptional reprogramming; tumor dormancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Dystrophin-Associated Proteins / genetics
  • Dystrophin-Associated Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasms / genetics
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-cbl / genetics
  • Proto-Oncogene Proteins c-cbl / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transplantation, Heterologous

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Dystrophin-Associated Proteins
  • MIRN190 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • Transcription Factors
  • syntrophin
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl