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Interleukin 8 is a biomarker of telomerase inhibition in cancer cells

BACKGROUND: Telomerase activity is required for both initiation and maintenance of tumorigenesis and over 90% cancers overexpress telomerase. Therefore, telomerase targeting has emerged as a potential strategy for cancer treatment. In agreement with this, several telomerase inhibitors are being test...

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Autores principales: Solomon, Peter, Dong, Yuying, Dogra, Shaillay, Gupta, Romi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038317/
https://www.ncbi.nlm.nih.gov/pubmed/29986697
http://dx.doi.org/10.1186/s12885-018-4633-x
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author Solomon, Peter
Dong, Yuying
Dogra, Shaillay
Gupta, Romi
author_facet Solomon, Peter
Dong, Yuying
Dogra, Shaillay
Gupta, Romi
author_sort Solomon, Peter
collection PubMed
description BACKGROUND: Telomerase activity is required for both initiation and maintenance of tumorigenesis and over 90% cancers overexpress telomerase. Therefore, telomerase targeting has emerged as a potential strategy for cancer treatment. In agreement with this, several telomerase inhibitors are being tested for cancer treatment and have shown some promise. However, because of the variability in response between the cancer patients, it is important to identify biomarkers that allow for distinguishing cancers that are responsive to telomerase inhibition from the cancers that are not. Therefore, in this study we performed experiments to identify a biomarker that can be used to predict telomerase inhibition induced tumor growth inhibition. METHODS: In our study, we have performed transcriptome-wide gene expression analysis on multiple ovarian and colon cancer cell lines that were treated with telomerase inhibitor imetelstat and were responsive to telomerase inhibition-induced tumor growth attenuation. RESULTS: We demonstrate that telomerase inhibition by telomerase inhibitor imetelstat results in decreased expression of interleukin 8 (IL8) in all telomerase responsive cancer cell lines. This phenomenon is of general occurrence because we find that multiple ovarian and colon cell lines show decrease in IL8 mRNA and protein levels after telomerase inhibition. Additionally, we find loss of IL8 phenocopy Telomerase inhibition mediated growth inhibitory effect in cancer cells. CONCLUSION: Taken together, our results show that IL8 is a biomarker that predict telomerase inhibition mediated growth attenuation of cancer cells and its loss phenocopy telomerase inhibition. Therefore, IL8 expression can be utilized as a biomarker for telomerase targeted cancer therapies to potentially predict therapeutic response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4633-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-60383172018-07-12 Interleukin 8 is a biomarker of telomerase inhibition in cancer cells Solomon, Peter Dong, Yuying Dogra, Shaillay Gupta, Romi BMC Cancer Research Article BACKGROUND: Telomerase activity is required for both initiation and maintenance of tumorigenesis and over 90% cancers overexpress telomerase. Therefore, telomerase targeting has emerged as a potential strategy for cancer treatment. In agreement with this, several telomerase inhibitors are being tested for cancer treatment and have shown some promise. However, because of the variability in response between the cancer patients, it is important to identify biomarkers that allow for distinguishing cancers that are responsive to telomerase inhibition from the cancers that are not. Therefore, in this study we performed experiments to identify a biomarker that can be used to predict telomerase inhibition induced tumor growth inhibition. METHODS: In our study, we have performed transcriptome-wide gene expression analysis on multiple ovarian and colon cancer cell lines that were treated with telomerase inhibitor imetelstat and were responsive to telomerase inhibition-induced tumor growth attenuation. RESULTS: We demonstrate that telomerase inhibition by telomerase inhibitor imetelstat results in decreased expression of interleukin 8 (IL8) in all telomerase responsive cancer cell lines. This phenomenon is of general occurrence because we find that multiple ovarian and colon cell lines show decrease in IL8 mRNA and protein levels after telomerase inhibition. Additionally, we find loss of IL8 phenocopy Telomerase inhibition mediated growth inhibitory effect in cancer cells. CONCLUSION: Taken together, our results show that IL8 is a biomarker that predict telomerase inhibition mediated growth attenuation of cancer cells and its loss phenocopy telomerase inhibition. Therefore, IL8 expression can be utilized as a biomarker for telomerase targeted cancer therapies to potentially predict therapeutic response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4633-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-09 /pmc/articles/PMC6038317/ /pubmed/29986697 http://dx.doi.org/10.1186/s12885-018-4633-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Solomon, Peter
Dong, Yuying
Dogra, Shaillay
Gupta, Romi
Interleukin 8 is a biomarker of telomerase inhibition in cancer cells
title Interleukin 8 is a biomarker of telomerase inhibition in cancer cells
title_full Interleukin 8 is a biomarker of telomerase inhibition in cancer cells
title_fullStr Interleukin 8 is a biomarker of telomerase inhibition in cancer cells
title_full_unstemmed Interleukin 8 is a biomarker of telomerase inhibition in cancer cells
title_short Interleukin 8 is a biomarker of telomerase inhibition in cancer cells
title_sort interleukin 8 is a biomarker of telomerase inhibition in cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038317/
https://www.ncbi.nlm.nih.gov/pubmed/29986697
http://dx.doi.org/10.1186/s12885-018-4633-x
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