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Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells

Overview of attention for article published in Molecular Cancer, October 2015
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Title
Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells
Published in
Molecular Cancer, October 2015
DOI 10.1186/s12943-015-0450-x
Pubmed ID
Authors

Shien Hu, Lan Liu, Eugene B. Chang, Jian-Ying Wang, Jean-Pierre Raufman

Abstract

Compromised colonic butyrate production resulting from low dietary fiber or altered gut microbiota may promote colon neoplasia. Previous reports indicate these actions are mediated in part by altered levels of miRNAs, including suppressed expression of the oncogenic miR-17-92a cluster. Here, we sought to identify the mechanisms underlying these effects of butyrate in colon cancer. miR-92a levels were measured in archived human colon cancer and adjacent normal colon specimens by microarray and quantitative RT-PCR (qPCR). The effects of butyrate and other histone deacetylase inhibitors (suberoylanilide hydroxamic acid (SAHA) and valproic acid) on primary (pri-miR17-92a), precursor and mature miR-92a were analyzed in HCT-116 and HT-29 human colon cancer cells using qPCR. The effects of butyrate, SAHA and valproic acid on protein levels of c-Myc, Drosha and p57 were measured in HCT-116 cells using immunoblotting. Regulation of C13orf25 promoter activity by butyrate was analyzed by luciferase reporter assay using modified pGL3 constructs containing a wild-type or mutated c-Myc binding site. Expression of c-Myc was modulated using siRNA or adenovirus vectors. p57 mRNA and protein were measured before and after transfection with miR-92a-mimic molecules. Following butyrate treatment and miR-92a-mimic transfection, apoptosis was analyzed by TUNEL staining and caspase-3 immunoblotting. Microarray, confirmed by qPCR, revealed a seven-fold increase in miR-92a levels in sporadic human colon cancer tissue compared to adjacent normal colon. Treating human colon cancer cells with butyrate reduced the levels of pri-miR17-92a, precursor and mature miR-92a, as well as c-Myc. SAHA and valproic acid had similar effects. Mutation of the c-Myc binding site diminished butyrate's inhibitory effects on C13orf25 promoter activity. Silencing c-Myc expression reduced miR-92a levels. c-Myc over-expression neutralized butyrate-induced attenuation of pri-miR17-92a. Exogenous miR-92a inhibited butyrate-induced p57 expression and reversed the beneficial actions of butyrate on colon cancer cell proliferation and apoptosis. Our findings identify a novel cellular mechanism whereby butyrate inhibits miR-92a transcription by reducing c-Myc, thus augmenting p57 levels. These actions diminish colon cancer cell proliferation and stimulate apoptosis. This newly described regulation of oncogenic miRNA biogenesis expands our understanding of colon cancer cell biology and identifies novel therapeutic targets.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 25%
Student > Master 11 23%
Unspecified 6 13%
Researcher 5 10%
Student > Bachelor 4 8%
Other 10 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 31%
Agricultural and Biological Sciences 10 21%
Unspecified 9 19%
Medicine and Dentistry 7 15%
Immunology and Microbiology 4 8%
Other 3 6%

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 22 October 2015.
All research outputs
#4,707,765
of 6,367,740 outputs
Outputs from Molecular Cancer
#455
of 653 outputs
Outputs of similar age
#133,825
of 196,964 outputs
Outputs of similar age from Molecular Cancer
#19
of 35 outputs
Altmetric has tracked 6,367,740 research outputs across all sources so far. This one is in the 14th percentile – i.e., 14% of other outputs scored the same or lower than it.
So far Altmetric has tracked 653 research outputs from this source. They receive a mean Attention Score of 3.1. This one is in the 14th percentile – i.e., 14% 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 196,964 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.