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Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer
Herein, we assess the gene expression changes activated in thyroid tumors through a computational approach, using the MapReduce algorithm. Through this predictive analysis, we identified the TfR1 gene as a critical mediator of thyroid tumor progression. Then, we investigated the effect of TfR1 gene...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033459/ https://www.ncbi.nlm.nih.gov/pubmed/32099899 http://dx.doi.org/10.1016/j.omto.2020.01.003 |
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author | Campisi, Agata Bonfanti, Roberta Raciti, Giuseppina Bonaventura, Gabriele Legnani, Laura Magro, Gaetano Pennisi, Marzio Russo, Giulia Chiacchio, Maria Assunta Pappalardo, Francesco Parenti, Rosalba |
author_facet | Campisi, Agata Bonfanti, Roberta Raciti, Giuseppina Bonaventura, Gabriele Legnani, Laura Magro, Gaetano Pennisi, Marzio Russo, Giulia Chiacchio, Maria Assunta Pappalardo, Francesco Parenti, Rosalba |
author_sort | Campisi, Agata |
collection | PubMed |
description | Herein, we assess the gene expression changes activated in thyroid tumors through a computational approach, using the MapReduce algorithm. Through this predictive analysis, we identified the TfR1 gene as a critical mediator of thyroid tumor progression. Then, we investigated the effect of TfR1 gene silencing through small interfering RNA (siRNA) in the expression of extracellular signal-regulated kinase 1/2 (Erk1/2) pathway and c-Myc in human differentiated follicular and undifferentiated anaplastic thyroid cancer. The expression levels of cyclin D(1), p53, and p27, proteins involved in cell cycle progression, were also evaluated. The effect of TfR1 gene silencing through siRNA on the apoptotic pathway activation was also tested. Computational prediction and in vitro studies demonstrate that TfR1 plays a key role in thyroid cancer and that its downregulation was able to inhibit the ERK pathway, reducing also c-Myc expression, which blocks the cell cycle and activates the apoptotic pathway. We demonstrate that TfR1 plays a crucial role for a rapid and transient activation of the ERK signaling pathway, which induces a deregulation of genes involved in the aberrant accumulation of intracellular free iron and in drug resistance. We also suggest that TfR1 might represent an important target for thyroid cancer therapy. |
format | Online Article Text |
id | pubmed-7033459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-70334592020-02-25 Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer Campisi, Agata Bonfanti, Roberta Raciti, Giuseppina Bonaventura, Gabriele Legnani, Laura Magro, Gaetano Pennisi, Marzio Russo, Giulia Chiacchio, Maria Assunta Pappalardo, Francesco Parenti, Rosalba Mol Ther Oncolytics Article Herein, we assess the gene expression changes activated in thyroid tumors through a computational approach, using the MapReduce algorithm. Through this predictive analysis, we identified the TfR1 gene as a critical mediator of thyroid tumor progression. Then, we investigated the effect of TfR1 gene silencing through small interfering RNA (siRNA) in the expression of extracellular signal-regulated kinase 1/2 (Erk1/2) pathway and c-Myc in human differentiated follicular and undifferentiated anaplastic thyroid cancer. The expression levels of cyclin D(1), p53, and p27, proteins involved in cell cycle progression, were also evaluated. The effect of TfR1 gene silencing through siRNA on the apoptotic pathway activation was also tested. Computational prediction and in vitro studies demonstrate that TfR1 plays a key role in thyroid cancer and that its downregulation was able to inhibit the ERK pathway, reducing also c-Myc expression, which blocks the cell cycle and activates the apoptotic pathway. We demonstrate that TfR1 plays a crucial role for a rapid and transient activation of the ERK signaling pathway, which induces a deregulation of genes involved in the aberrant accumulation of intracellular free iron and in drug resistance. We also suggest that TfR1 might represent an important target for thyroid cancer therapy. American Society of Gene & Cell Therapy 2020-01-21 /pmc/articles/PMC7033459/ /pubmed/32099899 http://dx.doi.org/10.1016/j.omto.2020.01.003 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Campisi, Agata Bonfanti, Roberta Raciti, Giuseppina Bonaventura, Gabriele Legnani, Laura Magro, Gaetano Pennisi, Marzio Russo, Giulia Chiacchio, Maria Assunta Pappalardo, Francesco Parenti, Rosalba Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer |
title | Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer |
title_full | Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer |
title_fullStr | Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer |
title_full_unstemmed | Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer |
title_short | Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer |
title_sort | gene silencing of transferrin-1 receptor as a potential therapeutic target for human follicular and anaplastic thyroid cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033459/ https://www.ncbi.nlm.nih.gov/pubmed/32099899 http://dx.doi.org/10.1016/j.omto.2020.01.003 |
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