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Therapy-induced stress response is associated with downregulation of pre-mRNA splicing in cancer cells

Overview of attention for article published in Genome Medicine, June 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (70th percentile)

Mentioned by

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4 tweeters
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1 patent

Citations

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17 Dimensions

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52 Mendeley
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Title
Therapy-induced stress response is associated with downregulation of pre-mRNA splicing in cancer cells
Published in
Genome Medicine, June 2018
DOI 10.1186/s13073-018-0557-y
Pubmed ID
Authors

Ksenia S. Anufrieva, Victoria О. Shender, Georgij P. Arapidi, Marat S. Pavlyukov, Michail I. Shakhparonov, Polina V. Shnaider, Ivan O. Butenko, Maria A. Lagarkova, Vadim M. Govorun

Abstract

Abnormal pre-mRNA splicing regulation is common in cancer, but the effects of chemotherapy on this process remain unclear. To evaluate the effect of chemotherapy on slicing regulation, we performed meta-analyses of previously published transcriptomic, proteomic, phosphoproteomic, and secretome datasets. Our findings were verified by LC-MS/MS, western blotting, immunofluorescence, and FACS analyses of multiple cancer cell lines treated with cisplatin and pladienolide B. Our results revealed that different types of chemotherapy lead to similar changes in alternative splicing by inducing intron retention in multiple genes. To determine the mechanism underlying this effect, we analyzed gene expression in 101 cell lines affected by ɣ-irradiation, hypoxia, and 10 various chemotherapeutic drugs. Strikingly, оnly genes involved in the cell cycle and pre-mRNA splicing regulation were changed in a similar manner in all 335 tested samples regardless of stress stimuli. We revealed significant downregulation of gene expression levels in these two pathways, which could be explained by the observed decrease in splicing efficiency and global intron retention. We showed that the levels of active spliceosomal proteins might be further post-translationally decreased by phosphorylation and export into the extracellular space. To further explore these bioinformatics findings, we performed proteomic analysis of cisplatin-treated ovarian cancer cells. Finally, we demonstrated that the splicing inhibitor pladienolide B impairs the cellular response to DNA damage and significantly increases the sensitivity of cancer cells to chemotherapy. Decreased splicing efficiency and global intron retention is a novel stress response mechanism that may promote survival of malignant cells following therapy. We found that this mechanism can be inhibited by pladienolide B, which significantly increases the sensitivity of cancer cells to cisplatin which makes it a good candidate drug for improving the efficiency of cancer therapy.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters 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 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 25%
Student > Bachelor 10 19%
Student > Ph. D. Student 9 17%
Student > Master 4 8%
Student > Doctoral Student 2 4%
Other 4 8%
Unknown 10 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 29%
Agricultural and Biological Sciences 8 15%
Medicine and Dentistry 4 8%
Neuroscience 2 4%
Psychology 2 4%
Other 7 13%
Unknown 14 27%

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 26 January 2022.
All research outputs
#5,104,507
of 20,975,194 outputs
Outputs from Genome Medicine
#898
of 1,340 outputs
Outputs of similar age
#87,120
of 296,861 outputs
Outputs of similar age from Genome Medicine
#1
of 1 outputs
Altmetric has tracked 20,975,194 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,340 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.5. This one is in the 32nd percentile – i.e., 32% 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 296,861 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
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