The microRNA landscape changes during the progression of cancer. We defined a metastasis-associated microRNA landscape using a systematic approach. We profiled and validated microRNA and mRNA expression in a unique series of human colorectal metastasis tissues together with their matched primary tumors and corresponding normal tissues. We identified an exclusive miRNA-signature that is differentially expressed in metastases. Three of these miRNAs were identified as key drivers of an EMT-regulating network acting though a number of novel targets. These targets include SIAH1, SETD2, ZEB2, and especially FOXN3, which we demonstrated for the first time as a direct transcriptional suppressor of N-cadherin. The modulation of N-cadherin expression had significant impact on migration, invasion, and metastasis in two different in vivo models. The significant deregulation of the microRNAs defined the network was confirmed in an independent patient set as well as in a database of diverse malignancies derived from more than 6000 patients. Our data defines a novel metastasis-orchestrating network based on systematic hypothesis generation from metastasis tissues.
Pharmacology, Toxicology and Pharmaceutical Science
1
2%
Nursing and Health Professions
1
2%
Other
1
2%
Unknown
14
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 June 2015.
All research outputs
#24,723,713
of 34,350,842 outputs
Outputs from Cancer Research
#32,026
of 35,807 outputs
Outputs of similar age
#199,934
of 301,847 outputs
Outputs of similar age from Cancer Research
#350
of 488 outputs
Altmetric has tracked 34,350,842 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 35,807 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one is in the 7th percentile – i.e., 7% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 301,847 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 488 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.
