↓ Skip to main content

Posttranscriptional upregulation of HER3 by HER2 mRNA induces trastuzumab resistance in breast cancer

Overview of attention for article published in Molecular Cancer, August 2018
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
19 Dimensions

Readers on

mendeley
30 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Posttranscriptional upregulation of HER3 by HER2 mRNA induces trastuzumab resistance in breast cancer
Published in
Molecular Cancer, August 2018
DOI 10.1186/s12943-018-0862-5
Pubmed ID
Authors

Xin Li, Yuxiu Xu, Yun Ding, Changfei Li, Hong Zhao, Jiandong Wang, Songdong Meng

Abstract

HER2 gene amplification generates an enormous number of HER2 transcripts, but the global effects on endogenous miRNA targets including HER family members in breast cancer are unexplored. We generated a HER2-3'UTR expressing vector to test the tumor-promoting properties in HER2 low expressing T47D and MCF7 cells. Through microarray analysis and real-time PCR analysis we identified genes that were regulated by HER2-3'UTR. Positive and negative manipulation of miRNA expression, response element mutational studies and transcript reporter assays were performed to explore the mechanism of competitive sequestration of miR125a/miRNA125b by HER2 3'UTR. To investigate if trastuzumab-induced upregulation of HER3 is also mediated through miRNA de-repression, we used the CRISPR/cas9 to mutate the endogenous HER2 mRNA in HER2 over-expressing Au565 cells. Finally, we looked at cohorts of breast cancer samples of our own and the TCGA to show if HER2 and HER3 mRNAs correlate with each other. The HER2 3'UTR pronouncedly promoted cell proliferation, colony formation, and breast tumor growth. High-throughput sequencing revealed a significant increase in HER3 mRNA and protein levels by the HER2 3'untranslated region (3'UTR). The HER2 3'UTR harboring a shared miR-125a/b response element induced miR-125a/b sequestration and thus resulted in HER3 mRNA derepression. Trastuzumab treatment upregulated HER3 via elevated HER2 mRNA expression, leading to trastuzumab resistance. Depletion of miR-125a/b enhanced the antitumor activity of trastuzumab. Microarray data from HER2-overexpressing primary breast cancer showed significant elevation of mRNAs for predicted miR-125a/b targets compared to non-targets. These results suggest that HER2 3'UTR-mediated HER3 upregulation is involved in breast cell transformation, increased tumor growth, and resistance to anti-HER2 therapy. The combinatorial targeting of HER3 mRNA or miR-125a/b may offer an effective tool for breast cancer therapy.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 13%
Student > Bachelor 4 13%
Researcher 3 10%
Student > Master 3 10%
Other 2 7%
Other 7 23%
Unknown 7 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 27%
Pharmacology, Toxicology and Pharmaceutical Science 4 13%
Agricultural and Biological Sciences 3 10%
Unspecified 2 7%
Medicine and Dentistry 2 7%
Other 5 17%
Unknown 6 20%

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 16 August 2018.
All research outputs
#10,647,216
of 13,381,625 outputs
Outputs from Molecular Cancer
#801
of 1,121 outputs
Outputs of similar age
#167,348
of 223,504 outputs
Outputs of similar age from Molecular Cancer
#1
of 1 outputs
Altmetric has tracked 13,381,625 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 1,121 research outputs from this source. They receive a mean Attention Score of 3.5. This one is in the 13th percentile – i.e., 13% 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 223,504 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.
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