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Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres

Overview of attention for article published in BMC Cancer, September 2008
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (81st percentile)

Mentioned by

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4 patents
wikipedia
1 Wikipedia page

Citations

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314 Dimensions

Readers on

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140 Mendeley
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1 CiteULike
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1 Connotea
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Title
Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres
Published in
BMC Cancer, September 2008
DOI 10.1186/1471-2407-8-266
Pubmed ID
Authors

Qing Ji, Xinbao Hao, Yang Meng, Min Zhang, Jeffrey DeSano, Daiming Fan, Liang Xu

Abstract

MicroRNAs (miRNAs), some of which function as oncogenes or tumor suppressor genes, are involved in carcinogenesis via regulating cell proliferation and/or cell death. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor. miR-34 targets Notch, HMGA2, and Bcl-2, genes involved in the self-renewal and survival of cancer stem cells. The role of miR-34 in gastric cancer has not been reported previously. In this study, we examined the effects of miR-34 restoration on p53-mutant human gastric cancer cells and potential target gene expression. Human gastric cancer cells were transfected with miR-34 mimics or infected with the lentiviral miR-34-MIF expression system, and validated by miR-34 reporter assay using Bcl-2 3'UTR reporter. Potential target gene expression was assessed by Western blot for proteins, and by quantitative real-time RT-PCR for mRNAs. The effects of miR-34 restoration were assessed by cell growth assay, cell cycle analysis, caspase-3 activation, and cytotoxicity assay, as well as by tumorsphere formation and growth. Human gastric cancer Kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. Bcl-2 3'UTR reporter assay showed that the transfected miR-34s were functional and confirmed that Bcl-2 is a direct target of miR-34. Restoration of miR-34 chemosensitized Kato III cells with a high level of Bcl-2, but not MKN-45 cells with a low level of Bcl-2. miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth. Our results demonstrate that in p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34 inhibits tumorsphere formation and growth, which is reported to be correlated to the self-renewal of cancer stem cells. The mechanism of miR-34-mediated suppression of self-renewal appears to be related to the direct modulation of downstream targets Bcl-2, Notch, and HMGA2, indicating that miR-34 may be involved in gastric cancer stem cell self-renewal/differentiation decision-making. Our study suggests that restoration of the tumor suppressor miR-34 may provide a novel molecular therapy for p53-mutant gastric cancer.

Mendeley readers

The data shown below were compiled from readership statistics for 140 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 <1%
United States 1 <1%
Denmark 1 <1%
Unknown 137 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 38 27%
Researcher 35 25%
Student > Master 15 11%
Student > Bachelor 14 10%
Student > Postgraduate 7 5%
Other 20 14%
Unknown 11 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 58 41%
Biochemistry, Genetics and Molecular Biology 28 20%
Medicine and Dentistry 25 18%
Engineering 4 3%
Computer Science 2 1%
Other 5 4%
Unknown 18 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. 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 19 November 2020.
All research outputs
#2,732,873
of 19,441,086 outputs
Outputs from BMC Cancer
#623
of 7,004 outputs
Outputs of similar age
#50,055
of 274,557 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
Altmetric has tracked 19,441,086 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,004 research outputs from this source. They receive a mean Attention Score of 4.1. This one has done particularly well, scoring higher than 90% of its peers.
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 274,557 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them