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NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells

Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically i...

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Autores principales: Savas, Sevtap, Azorsa, David O., Jarjanazi, Hamdi, Ibrahim-Zada, Irada, Gonzales, Irma M., Arora, Shilpi, Henderson, Meredith C., Choi, Yun Hee, Briollais, Laurent, Ozcelik, Hilmi, Tuzmen, Sukru
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070731/
https://www.ncbi.nlm.nih.gov/pubmed/21483694
http://dx.doi.org/10.1371/journal.pone.0018306
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author Savas, Sevtap
Azorsa, David O.
Jarjanazi, Hamdi
Ibrahim-Zada, Irada
Gonzales, Irma M.
Arora, Shilpi
Henderson, Meredith C.
Choi, Yun Hee
Briollais, Laurent
Ozcelik, Hilmi
Tuzmen, Sukru
author_facet Savas, Sevtap
Azorsa, David O.
Jarjanazi, Hamdi
Ibrahim-Zada, Irada
Gonzales, Irma M.
Arora, Shilpi
Henderson, Meredith C.
Choi, Yun Hee
Briollais, Laurent
Ozcelik, Hilmi
Tuzmen, Sukru
author_sort Savas, Sevtap
collection PubMed
description Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically identify the genes involved in resistance to cytotoxic effects of these two drugs in the NCI60 cell line panel. We used the pharmacological data available for all the NCI60 cell lines to classify simvastatin or lovastatin resistant and sensitive cell lines, respectively. Next, we performed whole-genome single marker case-control association tests for the lovastatin and simvastatin resistant and sensitive cells using their publicly available Affymetrix 125K SNP genomic data. The results were then evaluated using RNAi methodology. After correction of the p-values for multiple testing using False Discovery Rate, our results identified three genes (NRP1, COL13A1, MRPS31) and six genes (EAF2, ANK2, AKAP7, STEAP2, LPIN2, PARVB) associated with resistance to simvastatin and lovastatin, respectively. Functional validation using RNAi confirmed that silencing of EAF2 expression modulated the response of HCT-116 colon cancer cells to both statins. In summary, we have successfully utilized the publicly available data on the NCI60 cell lines to perform whole-genome association studies for simvastatin and lovastatin. Our results indicated genes involved in the cellular response to these statins and siRNA studies confirmed the role of the EAF2 in response to these drugs in HCT-116 colon cancer cells.
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spelling pubmed-30707312011-04-11 NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells Savas, Sevtap Azorsa, David O. Jarjanazi, Hamdi Ibrahim-Zada, Irada Gonzales, Irma M. Arora, Shilpi Henderson, Meredith C. Choi, Yun Hee Briollais, Laurent Ozcelik, Hilmi Tuzmen, Sukru PLoS One Research Article Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically identify the genes involved in resistance to cytotoxic effects of these two drugs in the NCI60 cell line panel. We used the pharmacological data available for all the NCI60 cell lines to classify simvastatin or lovastatin resistant and sensitive cell lines, respectively. Next, we performed whole-genome single marker case-control association tests for the lovastatin and simvastatin resistant and sensitive cells using their publicly available Affymetrix 125K SNP genomic data. The results were then evaluated using RNAi methodology. After correction of the p-values for multiple testing using False Discovery Rate, our results identified three genes (NRP1, COL13A1, MRPS31) and six genes (EAF2, ANK2, AKAP7, STEAP2, LPIN2, PARVB) associated with resistance to simvastatin and lovastatin, respectively. Functional validation using RNAi confirmed that silencing of EAF2 expression modulated the response of HCT-116 colon cancer cells to both statins. In summary, we have successfully utilized the publicly available data on the NCI60 cell lines to perform whole-genome association studies for simvastatin and lovastatin. Our results indicated genes involved in the cellular response to these statins and siRNA studies confirmed the role of the EAF2 in response to these drugs in HCT-116 colon cancer cells. Public Library of Science 2011-04-04 /pmc/articles/PMC3070731/ /pubmed/21483694 http://dx.doi.org/10.1371/journal.pone.0018306 Text en Savas et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Savas, Sevtap
Azorsa, David O.
Jarjanazi, Hamdi
Ibrahim-Zada, Irada
Gonzales, Irma M.
Arora, Shilpi
Henderson, Meredith C.
Choi, Yun Hee
Briollais, Laurent
Ozcelik, Hilmi
Tuzmen, Sukru
NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells
title NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells
title_full NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells
title_fullStr NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells
title_full_unstemmed NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells
title_short NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells
title_sort nci60 cancer cell line panel data and rnai analysis help identify eaf2 as a modulator of simvastatin and lovastatin response in hct-116 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070731/
https://www.ncbi.nlm.nih.gov/pubmed/21483694
http://dx.doi.org/10.1371/journal.pone.0018306
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