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The miR-487b-3p/GRM3/TGFβ signaling axis is an important regulator of colon cancer tumorigenesis

Overview of attention for article published in Oncogene, January 2017
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Title
The miR-487b-3p/GRM3/TGFβ signaling axis is an important regulator of colon cancer tumorigenesis
Published in
Oncogene, January 2017
DOI 10.1038/onc.2016.499
Pubmed ID
Authors

H Yi, L Geng, A Black, G Talmon, L Berim, J Wang

Abstract

Molecular targeting is an import strategy to treat advanced colon cancer. The current study demonstrates that expression of GRM3, a metabotropic glutamate receptor mainly expressed in mammalian central nervous system, is significantly upregulated in majority of human colonic adenocarcinomas tested and colon cancer cell lines. Knockdown of GRM3 expression or inhibition of GRM3 activation in colon cancer cells reduces cell survival and anchorage-independent growth in vitro and inhibits tumor growth in vivo. Mechanistically, GRM3 antagonizes TGFβ-mediated activation of protein kinase A and inhibition of Protein kinase B (AKT). In addition, TGFβ signaling increases GRM3 protein stability and knockdown of GRM3 enhances TGFβ-mediated tumor suppressor function. Further studies indicate that miR-487b-3p directly targets GRM3. Overexpression of miR-487b-3p mimics the effects of GRM3 knockdown and suppresses the tumorigenicity of colon cancer cells in vivo. Expression of miR-487b-3p is decreased in colon adenocarcinomas and inversely correlates with GRM3 expression. Taken together, these studies indicate that upregulation of GRM3 expression is a functionally important molecular event in colon cancer, and that GRM3 is a promising molecular target for colon cancer treatment. This is particularly interesting and important from a therapeutic standpoint because numerous metabotropic glutamate receptor antagonists are available, many of which have been found unsuitable for treatment of neuropsychiatric disorders for reasons such as inability to readily penetrate blood brain barriers. As GRM3 is upregulated in colon cancer, but rarely expressed in normal peripheral tissues, targeting GRM3 with such agents would not likely cause adverse neurological or peripheral side effects, making GRM3 an attractive and specific molecular target for colon cancer treatment.Oncogene advance online publication, 23 January 2017; doi:10.1038/onc.2016.499.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 23%
Researcher 4 18%
Student > Bachelor 2 9%
Student > Ph. D. Student 1 5%
Unknown 10 45%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 23%
Biochemistry, Genetics and Molecular Biology 2 9%
Medicine and Dentistry 2 9%
Nursing and Health Professions 1 5%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Other 1 5%
Unknown 10 45%
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 31 January 2017.
All research outputs
#17,870,599
of 22,947,506 outputs
Outputs from Oncogene
#9,455
of 10,663 outputs
Outputs of similar age
#292,530
of 419,040 outputs
Outputs of similar age from Oncogene
#74
of 102 outputs
Altmetric has tracked 22,947,506 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 10,663 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one is in the 9th percentile – i.e., 9% 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 419,040 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 102 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.