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MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy

Overview of attention for article published in Molecular Cancer, December 2015
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Title
MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy
Published in
Molecular Cancer, December 2015
DOI 10.1186/s12943-015-0480-4
Pubmed ID
Authors

Xinfeng Yu, Aiping Luo, Yicong Liu, Shuqing Wang, Ye Li, Wenna Shi, Zhihua Liu, Xianjun Qu

Abstract

Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER(+)) breast cancers. However, the development of endocrine resistance is the impediment for successful treatment. We aimed to explore the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. Experiments were performed in ER(+) and estrogen/TAM-sensitive MCF7 cells and antiestrogen-resistant MCF7/LCC9 cells. The expression of miR-214 and uncoupling protein 2 (UCP2) was determined by RT-qPCR and Western blot in breast cancer cells and human breast cancer tissue specimens. Cell autophagy was examined by fluorescent probe monodansyl cadaverine (MDC) and GFP-LC3-II-positive punctate identified by confocal microscopy. Apoptotic cells were determined by Annexin V-FITC/PI staining. The potential regulatory target of miR-214 was determined by prediction tool, target protein expression and luciferase reporter assay. 4-OHT/FUL treatment resulted in induction of apoptosis as well as autophagy in breast cancer cells. Autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. MiR-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL-induced apoptosis through inhibition of autophagy. Importantly, a negative correlation was established between miR-214 and UCP2 in human breast cancer tissue specimens assayed by RT-qPCR. UCP2 was identified to be a direct target of miR-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3K-Akt-mTOR pathway, thereby inducing autophagy by overexpression of UCP2. MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through inhibition of autophagy by targeting UCP2. MiR-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER(+) breast cancers.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
China 1 2%
Unknown 45 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 20%
Student > Master 6 13%
Researcher 5 11%
Professor 3 7%
Student > Bachelor 2 4%
Other 7 15%
Unknown 14 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 20%
Agricultural and Biological Sciences 8 17%
Medicine and Dentistry 6 13%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Immunology and Microbiology 2 4%
Other 5 11%
Unknown 14 30%
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 17 December 2015.
All research outputs
#18,432,465
of 22,835,198 outputs
Outputs from Molecular Cancer
#1,291
of 1,721 outputs
Outputs of similar age
#281,669
of 390,233 outputs
Outputs of similar age from Molecular Cancer
#22
of 38 outputs
Altmetric has tracked 22,835,198 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 1,721 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. 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 390,233 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 38 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.