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The long noncoding RNA H19 promotes tamoxifen resistance in breast cancer via autophagy

Overview of attention for article published in Journal of Hematology & Oncology, July 2019
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Title
The long noncoding RNA H19 promotes tamoxifen resistance in breast cancer via autophagy
Published in
Journal of Hematology & Oncology, July 2019
DOI 10.1186/s13045-019-0747-0
Pubmed ID
Authors

Ji Wang, Shuduo Xie, Jingjing Yang, Hanchu Xiong, Yunlu Jia, Yulu Zhou, Yongxia Chen, Xiaogang Ying, Cong Chen, Chenyang Ye, Linbo Wang, Jichun Zhou

Abstract

Tamoxifen resistance remains a clinical challenge for hormone receptor-positive breast cancer. Recently, dysregulations in autophagy have been suggested as a potential mechanism for tamoxifen resistance. Although the long noncoding RNA H19 is involved in various stages of tumorigenesis, its role in tamoxifen resistance remains unknown. Here, we assessed the role of H19 in the development of tamoxifen-resistant breast cancer. Quantitative real-time PCR analyzed expression of H19 in tamoxifen-resistant breast cancer tissues. Knockdown of H19 was used to assess the sensitivity to tamoxifen in vitro and in vivo. Both knockdown and overexpression of H19 were used to analyze the status of autophagy. Real-time quantitative methylation-specific polymerase chain reaction, chromatin immunoprecipitation, immunofluorescence, and Western blot were used to explore the tamoxifen resistance mechanism of H19. In this study, we observed that the expression of H19 was substantially upregulated in tamoxifen-resistant breast cancer cell line and tumor tissues, and knockdown of H19 enhanced the sensitivity to tamoxifen both in vitro and in vivo. Furthermore, knockdown of H19 significantly inhibited autophagy in MCF7 tamoxifen-resistant (MCF7/TAMR) cells. Conversely, overexpression of H19 promoted autophagy. Interestingly, overexpression of H19 in MCF7 tamoxifen-sensitive cells could recapitulate tamoxifen resistance. Moreover, an increase in methylation in the promoter region of Beclin1 was observed in MCF7/TAMR-shH19 cells. In the double knockdown groups, both shH19+shSAHH and shH19+shDNMT3B rescued the Beclin1 promoter region methylation levels and reactivated autophagy functions. A chromatin immunoprecipitation assay further validated that DNMT3B binds to the Beclin1 promoter region and the knockdown of H19 increases this binding. Our findings demonstrate that H19 induces autophagy activation via the H19/SAHH/DNMT3B axis, which could contribute to tamoxifen resistance in breast cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 75 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 16%
Student > Master 8 11%
Researcher 6 8%
Student > Doctoral Student 5 7%
Student > Bachelor 5 7%
Other 9 12%
Unknown 30 40%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 23 31%
Medicine and Dentistry 8 11%
Agricultural and Biological Sciences 4 5%
Immunology and Microbiology 4 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 4 5%
Unknown 30 40%
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 28 July 2019.
All research outputs
#18,686,631
of 23,153,184 outputs
Outputs from Journal of Hematology & Oncology
#935
of 1,202 outputs
Outputs of similar age
#258,136
of 346,463 outputs
Outputs of similar age from Journal of Hematology & Oncology
#28
of 32 outputs
Altmetric has tracked 23,153,184 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 1,202 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.4. This one is in the 12th percentile – i.e., 12% 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 346,463 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.