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...

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Autores principales: Kim, Kyounghyun, Chadalapaka, Gayathri, Lee, Syng-ook, Yamada, Daisuke, Sastre-Garau, Xavier, Defossez, Pierre-Antoine, Park, Yun-Yong, Lee, Ju-Seog, Safe, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
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.
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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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