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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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/7683817 |
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| author | Graciela Ruiz Heriberto A. Valencia-González Delia Pérez-Montiel Felipe Muñoz Rodolfo Ocadiz-Delgado Jorge Fernández-Retana Carlos Pérez-Plasencia Osbaldo Reséndis-Antonio Patricio Gariglio Alejandro García-Carrancá |
| author_facet | Graciela Ruiz Heriberto A. Valencia-González Delia Pérez-Montiel Felipe Muñoz Rodolfo Ocadiz-Delgado Jorge Fernández-Retana Carlos Pérez-Plasencia Osbaldo Reséndis-Antonio Patricio Gariglio Alejandro García-Carrancá |
| author_sort | Graciela Ruiz |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-fdf24b4eb1b84f9dac956679f750b3a1 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-fdf24b4eb1b84f9dac956679f750b3a12025-02-03T07:23:36ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/76838177683817Genes 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 LineGraciela Ruiz0Heriberto A. Valencia-González1Delia Pérez-Montiel2Felipe Muñoz3Rodolfo Ocadiz-Delgado4Jorge Fernández-Retana5Carlos Pérez-Plasencia6Osbaldo Reséndis-Antonio7Patricio Gariglio8Alejandro García-Carrancá9Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico City, MexicoPrograma de Maestría y Doctorado en Ciencias Bioquímicas, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, MexicoDepartamento de Patología, Instituto Nacional de Cancerología, Secretaría de Salud, Mexico City, MexicoHuman Systems Biology Laboratory, Instituto Nacional de Medicina Genómica & Coordinación de la Investigación Científica, Red de Apoyo a la Investigación-Universidad Nacional Autónoma de México, Mexico City, MexicoDepartamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico City, MexicoDepartment of Natural Science, Universidad Autonoma Metropolitana, Cuajimalpa, Mexico City, MexicoUnidad de Investigación Biomédica en Cáncer, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México & Instituto Nacional de Cancerología, Secretaría de Salud, Mexico City, MexicoHuman Systems Biology Laboratory, Instituto Nacional de Medicina Genómica & Coordinación de la Investigación Científica, Red de Apoyo a la Investigación-Universidad Nacional Autónoma de México, Mexico City, MexicoDepartamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico City, MexicoUnidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México & Instituto Nacional de Cancerología, Secretaría de Salud, Mexico City, MexicoTranscription 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.http://dx.doi.org/10.1155/2019/7683817 |
| spellingShingle | Graciela Ruiz Heriberto A. Valencia-González Delia Pérez-Montiel Felipe Muñoz Rodolfo Ocadiz-Delgado Jorge Fernández-Retana Carlos Pérez-Plasencia Osbaldo Reséndis-Antonio Patricio Gariglio Alejandro García-Carrancá 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 Stem Cells International |
| 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 |
| url | http://dx.doi.org/10.1155/2019/7683817 |
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