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Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line

Transcription factors OCT4, SOX2, KLF4, C-MYC, and NANOG (OSKM-N) regulate pluripotency and stemness, and their ectopic expression reprograms human and murine fibroblasts that constitute the key of regenerative medicine. To determine their contribution to cell transformation, we analyzed the gene ex...

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Autores principales: Ruiz, Graciela, Valencia-González, Heriberto A., Pérez-Montiel, Delia, Muñoz, Felipe, Ocadiz-Delgado, Rodolfo, Fernández-Retana, Jorge, Pérez-Plasencia, Carlos, Reséndis-Antonio, Osbaldo, Gariglio, Patricio, García-Carrancá, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914900/
https://www.ncbi.nlm.nih.gov/pubmed/31885625
http://dx.doi.org/10.1155/2019/7683817
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author Ruiz, Graciela
Valencia-González, Heriberto A.
Pérez-Montiel, Delia
Muñoz, Felipe
Ocadiz-Delgado, Rodolfo
Fernández-Retana, Jorge
Pérez-Plasencia, Carlos
Reséndis-Antonio, Osbaldo
Gariglio, Patricio
García-Carrancá, Alejandro
author_facet Ruiz, Graciela
Valencia-González, Heriberto A.
Pérez-Montiel, Delia
Muñoz, Felipe
Ocadiz-Delgado, Rodolfo
Fernández-Retana, Jorge
Pérez-Plasencia, Carlos
Reséndis-Antonio, Osbaldo
Gariglio, Patricio
García-Carrancá, Alejandro
author_sort Ruiz, Graciela
collection PubMed
description Transcription factors OCT4, SOX2, KLF4, C-MYC, and NANOG (OSKM-N) regulate pluripotency and stemness, and their ectopic expression reprograms human and murine fibroblasts that constitute the key of regenerative medicine. To determine their contribution to cell transformation, we analyzed the gene expression profiles of these transcription factors in cervical cancer samples and found that they are preferentially expressed in the tumor component. Also, cancer stem cell-enriched cultures grown as sphere cultures showed overexpression of OSKM-N genes. Importantly, we observed that lentiviral-mediated transduction of these factors confers, to a nontumorigenic immortalized human cell line, properties of cancer stem cells as the ability to form tumors in a mouse model. When we performed a meta-analysis using microarray data from cervical cancer biopsies and normal tissues, we found that the expression of OSKM-N and some target genes allowed separating tumor and normal tissues between samples, which enhanced the importance of OSKM-N in the tumorigenesis. Finally, we analyzed and compared both transcript and protein expression profiles of these factors within a cohort of patients with cervical cancer. To our knowledge, this is the first time that the expression of OSKM-N is described to induce one of the main characteristics of the cancer stem cell, the tumorigenicity. And, more importantly, its exogenous expression in a nontumorigenic cell line is sufficient to induce a tumorigenic phenotype; furthermore, the differential expression of this transcription factor distinguishes tumor tissue and normal tissue in cervical samples.
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spelling pubmed-69149002019-12-29 Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line Ruiz, Graciela Valencia-González, Heriberto A. Pérez-Montiel, Delia Muñoz, Felipe Ocadiz-Delgado, Rodolfo Fernández-Retana, Jorge Pérez-Plasencia, Carlos Reséndis-Antonio, Osbaldo Gariglio, Patricio García-Carrancá, Alejandro Stem Cells Int Research Article Transcription factors OCT4, SOX2, KLF4, C-MYC, and NANOG (OSKM-N) regulate pluripotency and stemness, and their ectopic expression reprograms human and murine fibroblasts that constitute the key of regenerative medicine. To determine their contribution to cell transformation, we analyzed the gene expression profiles of these transcription factors in cervical cancer samples and found that they are preferentially expressed in the tumor component. Also, cancer stem cell-enriched cultures grown as sphere cultures showed overexpression of OSKM-N genes. Importantly, we observed that lentiviral-mediated transduction of these factors confers, to a nontumorigenic immortalized human cell line, properties of cancer stem cells as the ability to form tumors in a mouse model. When we performed a meta-analysis using microarray data from cervical cancer biopsies and normal tissues, we found that the expression of OSKM-N and some target genes allowed separating tumor and normal tissues between samples, which enhanced the importance of OSKM-N in the tumorigenesis. Finally, we analyzed and compared both transcript and protein expression profiles of these factors within a cohort of patients with cervical cancer. To our knowledge, this is the first time that the expression of OSKM-N is described to induce one of the main characteristics of the cancer stem cell, the tumorigenicity. And, more importantly, its exogenous expression in a nontumorigenic cell line is sufficient to induce a tumorigenic phenotype; furthermore, the differential expression of this transcription factor distinguishes tumor tissue and normal tissue in cervical samples. Hindawi 2019-12-01 /pmc/articles/PMC6914900/ /pubmed/31885625 http://dx.doi.org/10.1155/2019/7683817 Text en Copyright © 2019 Graciela Ruiz et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ruiz, Graciela
Valencia-González, Heriberto A.
Pérez-Montiel, Delia
Muñoz, Felipe
Ocadiz-Delgado, Rodolfo
Fernández-Retana, Jorge
Pérez-Plasencia, Carlos
Reséndis-Antonio, Osbaldo
Gariglio, Patricio
García-Carrancá, Alejandro
Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line
title Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line
title_full Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line
title_fullStr Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line
title_full_unstemmed Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line
title_short Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line
title_sort genes involved in the transcriptional regulation of pluripotency are expressed in malignant tumors of the uterine cervix and can induce tumorigenic capacity in a nontumorigenic cell line
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914900/
https://www.ncbi.nlm.nih.gov/pubmed/31885625
http://dx.doi.org/10.1155/2019/7683817
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