IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER
The human POK family members are transcription factors with a POZ domain and zinc fingers that act primarily as transcriptional repressors. Several members of this family are involved in oncogenesis and this prompted us to assess whether expression levels of individual POK family members are associa...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288192/ https://www.ncbi.nlm.nih.gov/pubmed/21765466 http://dx.doi.org/10.1038/onc.2011.296 |
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author | Kim, Kyounghyun Chadalapaka, Gayathri Lee, Syng-ook Yamada, Daisuke Sastre-Garau, Xavier Defossez, Pierre-Antoine Park, Yun-Yong Lee, Ju-Seog Safe, Stephen |
author_facet | Kim, Kyounghyun Chadalapaka, Gayathri Lee, Syng-ook Yamada, Daisuke Sastre-Garau, Xavier Defossez, Pierre-Antoine Park, Yun-Yong Lee, Ju-Seog Safe, Stephen |
author_sort | Kim, Kyounghyun |
collection | PubMed |
description | The human POK family members are transcription factors with a POZ domain and zinc fingers that act primarily as transcriptional repressors. Several members of this family are involved in oncogenesis and this prompted us to assess whether expression levels of individual POK family members are associated with clinical outcomes in cancer. We have observed that ZBTB4 is downregulated in breast cancer patients, and that its expression is significantly correlated with relapse-free survival. Further integrative analysis of mRNA and microRNA (miR) expression data from the NCI-60 cell lines revealed an inverse correlation between ZBTB4 and oncogenic miRs derived from the miR-17-92 cluster and its paralogues. The experimental results using MDA-MB-231 and MCF-7 human breast cancer cells confirm that miRNAs derived from these clusters, containing miR-17-5p, miR-20a, miR-106a, miR-106b and miR-93, negatively regulate ZBTB4 expression. Overexpression of ZBTB4 or restoration of ZBTB4 by using an antagomir inhibit growth and invasion of breast cancer cells, and this effect is due, in part, to ZBTB4-dependent repression of the specificity protein 1 (Sp1), Sp3, and Sp4 genes, and subsequent downregulation of several Sp-dependent oncogenes, in part, through competition between ZBTB4 and Sp transcription factors for GC-rich promoter sequences. These results confirm that ZBTB4 functions as a novel tumor suppressor gene with prognostic significance for breast cancer survival, and the oncogenic miR-17-92/ZBTB4/Sp axis may be a potential therapeutic target. |
format | Online Article Text |
id | pubmed-3288192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-32881922012-08-23 IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER Kim, Kyounghyun Chadalapaka, Gayathri Lee, Syng-ook Yamada, Daisuke Sastre-Garau, Xavier Defossez, Pierre-Antoine Park, Yun-Yong Lee, Ju-Seog Safe, Stephen Oncogene Article The human POK family members are transcription factors with a POZ domain and zinc fingers that act primarily as transcriptional repressors. Several members of this family are involved in oncogenesis and this prompted us to assess whether expression levels of individual POK family members are associated with clinical outcomes in cancer. We have observed that ZBTB4 is downregulated in breast cancer patients, and that its expression is significantly correlated with relapse-free survival. Further integrative analysis of mRNA and microRNA (miR) expression data from the NCI-60 cell lines revealed an inverse correlation between ZBTB4 and oncogenic miRs derived from the miR-17-92 cluster and its paralogues. The experimental results using MDA-MB-231 and MCF-7 human breast cancer cells confirm that miRNAs derived from these clusters, containing miR-17-5p, miR-20a, miR-106a, miR-106b and miR-93, negatively regulate ZBTB4 expression. Overexpression of ZBTB4 or restoration of ZBTB4 by using an antagomir inhibit growth and invasion of breast cancer cells, and this effect is due, in part, to ZBTB4-dependent repression of the specificity protein 1 (Sp1), Sp3, and Sp4 genes, and subsequent downregulation of several Sp-dependent oncogenes, in part, through competition between ZBTB4 and Sp transcription factors for GC-rich promoter sequences. These results confirm that ZBTB4 functions as a novel tumor suppressor gene with prognostic significance for breast cancer survival, and the oncogenic miR-17-92/ZBTB4/Sp axis may be a potential therapeutic target. 2011-07-18 2012-02-23 /pmc/articles/PMC3288192/ /pubmed/21765466 http://dx.doi.org/10.1038/onc.2011.296 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Kim, Kyounghyun Chadalapaka, Gayathri Lee, Syng-ook Yamada, Daisuke Sastre-Garau, Xavier Defossez, Pierre-Antoine Park, Yun-Yong Lee, Ju-Seog Safe, Stephen IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER |
title | IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER |
title_full | IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER |
title_fullStr | IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER |
title_full_unstemmed | IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER |
title_short | IDENTIFICATION OF ONCOGENIC MicroRNA-17-92/ZBTB4/SPECIFICITY PROTEIN AXIS IN BREAST CANCER |
title_sort | identification of oncogenic microrna-17-92/zbtb4/specificity protein axis in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288192/ https://www.ncbi.nlm.nih.gov/pubmed/21765466 http://dx.doi.org/10.1038/onc.2011.296 |
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