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Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells

Overview of attention for article published in Frontiers in Pharmacology, March 2016
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Title
Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells
Published in
Frontiers in Pharmacology, March 2016
DOI 10.3389/fphar.2016.00081
Pubmed ID
Authors

Jane Ying-Chieh Lee, Ching-Wen Kuo, Shing-Ling Tsai, Siao Muk Cheng, Shang-Hung Chen, Hsiu-Han Chan, Chun-Hui Lin, Kun-Yuan Lin, Chien-Feng Li, Jagat R. Kanwar, Euphemia Y. Leung, Carlos Chun Ho Cheung, Wei-Jan Huang, Yi-Ching Wang, Chun Hei Antonio Cheung

Abstract

SAHA is a class I HDAC/HDAC6 co-inhibitor and an autophagy inducer currently undergoing clinical investigations in breast cancer patients. However, the molecular mechanism of action of SAHA in breast cancer cells remains unclear. In this study, we found that SAHA is equally effective in targeting cells of different breast cancer subtypes and tamoxifen sensitivity. Importantly, we found that down-regulation of survivin plays an important role in SAHA-induced autophagy and cell viability reduction in human breast cancer cells. SAHA decreased survivin and XIAP gene transcription, induced survivin protein acetylation and early nuclear translocation in MCF7 and MDA-MB-231 breast cancer cells. It also reduced survivin and XIAP protein stability in part through modulating the expression and activation of the 26S proteasome and heat-shock protein 90. Interestingly, targeting HDAC3 and HDAC6, but not other HDAC isoforms, by siRNA/pharmacological inhibitors mimicked the effects of SAHA in modulating the acetylation, expression, and nuclear translocation of survivin and induced autophagy in MCF7 and MDA-MB-231 cancer cells. Targeting HDAC3 also mimicked the effect of SAHA in up-regulating the expression and activity of proteasome, which might lead to the reduced protein stability of survivin in breast cancer cells. In conclusion, this study provides new insights into SAHA's molecular mechanism of actions in breast cancer cells. Our findings emphasize the complexity of the regulatory roles in different HDAC isoforms and potentially assist in predicting the mechanism of novel HDAC inhibitors in targeted or combinational therapies in the future.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 1 3%
Unknown 37 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 21%
Professor 5 13%
Student > Ph. D. Student 5 13%
Researcher 4 11%
Student > Bachelor 3 8%
Other 5 13%
Unknown 8 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 26%
Agricultural and Biological Sciences 7 18%
Medicine and Dentistry 3 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Chemistry 2 5%
Other 6 16%
Unknown 8 21%
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 12 April 2016.
All research outputs
#18,449,393
of 22,858,915 outputs
Outputs from Frontiers in Pharmacology
#8,269
of 16,130 outputs
Outputs of similar age
#220,314
of 301,001 outputs
Outputs of similar age from Frontiers in Pharmacology
#56
of 94 outputs
Altmetric has tracked 22,858,915 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,130 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 37th percentile – i.e., 37% 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 301,001 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 94 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.