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Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma.

Publication ,  Journal Article
Mito, JK; Min, HD; Ma, Y; Carter, JE; Brigman, BE; Dodd, L; Dankort, D; McMahon, M; Kirsch, DG
Published in: J Pathol
January 2013

Undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue malignancies. Patients with large, high-grade sarcomas often develop fatal lung metastases. Understanding the mechanisms underlying sarcoma metastasis is needed to improve treatment of these patients. Micro-RNAs (miRNAs) are a class of small RNAs that post-transcriptionally regulate gene expression. Global alterations in miRNAs are frequently observed in a number of disease states including cancer. The signalling pathways that regulate miRNA biogenesis are beginning to emerge. To test the relevance of specific oncogenic mutations in miRNA biogenesis in sarcoma, we used primary soft tissue sarcomas expressing either Braf(V600E) or Kras(G12D). We found that Braf(V600E) mutant tumours, which have increased MAPK signalling, have higher levels of mature miRNAs and enhanced miRNA processing. To investigate the relevance of oncogene-dependent alterations in miRNA biogenesis, we introduced conditional mutations in Dicer and showed that Dicer haploinsufficiency promotes the development of distant metastases in an oncogene-dependent manner. These results demonstrate that a specific oncogenic mutation can cooperate with mutation in Dicer to promote tumour progression in vivo.

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Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

January 2013

Volume

229

Issue

1

Start / End Page

132 / 140

Location

England

Related Subject Headings

  • Time Factors
  • Soft Tissue Neoplasms
  • Sarcoma
  • Ribonuclease III
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins B-raf
  • Pathology
  • Neoplasm Invasiveness
  • Mutation
  • MicroRNAs
 

Citation

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Mito, J. K., Min, H. D., Ma, Y., Carter, J. E., Brigman, B. E., Dodd, L., … Kirsch, D. G. (2013). Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma. J Pathol, 229(1), 132–140. https://doi.org/10.1002/path.4099
Mito, Jeffrey K., Hooney D. Min, Yan Ma, Jessica E. Carter, Brian E. Brigman, Leslie Dodd, David Dankort, Martin McMahon, and David G. Kirsch. “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma.J Pathol 229, no. 1 (January 2013): 132–40. https://doi.org/10.1002/path.4099.
Mito JK, Min HD, Ma Y, Carter JE, Brigman BE, Dodd L, et al. Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma. J Pathol. 2013 Jan;229(1):132–40.
Mito, Jeffrey K., et al. “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma.J Pathol, vol. 229, no. 1, Jan. 2013, pp. 132–40. Pubmed, doi:10.1002/path.4099.
Mito JK, Min HD, Ma Y, Carter JE, Brigman BE, Dodd L, Dankort D, McMahon M, Kirsch DG. Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma. J Pathol. 2013 Jan;229(1):132–140.
Journal cover image

Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

January 2013

Volume

229

Issue

1

Start / End Page

132 / 140

Location

England

Related Subject Headings

  • Time Factors
  • Soft Tissue Neoplasms
  • Sarcoma
  • Ribonuclease III
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins B-raf
  • Pathology
  • Neoplasm Invasiveness
  • Mutation
  • MicroRNAs