MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer.

Genes Dev
Authors
Keywords
Abstract

While altered expression of microRNAs (miRs) in tumors has been well documented, it remains unclear how the miR transcriptome intersects neoplastic progression. By profiling the miR transcriptome we identified miR expression signatures associated with steps in tumorigenesis and the acquisition of hallmark capabilities in a prototypical mouse model of cancer. Metastases and a rare subset of primary tumors shared a distinct miR signature, implicating a discrete lineage for metastatic tumors. The miR-200 family is strongly down-regulated in metastases and met-like primary tumors, thereby relieving repression of the mesenchymal transcription factor Zeb1, which in turn suppresses E-cadherin. Treatment with a clinically approved angiogenesis inhibitor normalized angiogenic signature miRs in primary tumors, while altering expression of metastatic signature miRs similarly to liver metastases, suggesting their involvement in adaptive resistance to anti-angiogenic therapy via enhanced metastasis. Many of the miR changes associated with specific stages and hallmark capabilities in the mouse model are similarly altered in human tumors, including cognate pancreatic neuroendocrine tumors, implying a generality.

Year of Publication
2009
Journal
Genes Dev
Volume
23
Issue
18
Pages
2152-65
Date Published
2009 Sep 15
ISSN
1549-5477
URL
DOI
10.1101/gad.1820109
PubMed ID
19759263
PubMed Central ID
PMC2751988
Links
Grant list
T32 CA009043 / CA / NCI NIH HHS / United States
T32 CA09043 / CA / NCI NIH HHS / United States