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Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer

Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 is a nuclear receptor coregulator that is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer patients. Here, we show that PELP1 m...

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Autores principales: Roy, Sudipa Saha, Gonugunta, Vijaya Kumar, Bandyopadhyay, Abhik, Rao, Manjeet K, Goodall, Gregory J, Sun, LuZhe, Tekmal, Rajeshwar R, Vadlamudi, Ratna K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935988/
https://www.ncbi.nlm.nih.gov/pubmed/23975430
http://dx.doi.org/10.1038/onc.2013.332
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author Roy, Sudipa Saha
Gonugunta, Vijaya Kumar
Bandyopadhyay, Abhik
Rao, Manjeet K
Goodall, Gregory J
Sun, LuZhe
Tekmal, Rajeshwar R
Vadlamudi, Ratna K
author_facet Roy, Sudipa Saha
Gonugunta, Vijaya Kumar
Bandyopadhyay, Abhik
Rao, Manjeet K
Goodall, Gregory J
Sun, LuZhe
Tekmal, Rajeshwar R
Vadlamudi, Ratna K
author_sort Roy, Sudipa Saha
collection PubMed
description Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 is a nuclear receptor coregulator that is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer patients. Here, we show that PELP1 modulates expression of metastasis-influencing microRNAs (miRs) to promote cancer metastasis. Whole genome miR array analysis using PELP1 over expressing and under expressing model cells revealed that miR-200a and miR-141 levels inversely correlated with PELP1 expression. Consistent with this, PELP1 knockdown resulted in lower expression of miR-200a target genes ZEB1 and ZEB2. PELP1 knockdown significantly reduced tumor growth and metastasis compared with parental cells in an orthotopic xenograft tumor model. Furthermore, re-introduction of miR-200a and miR-141 mimetics into PELP1 overexpressing cells reversed PELP1 target gene expression, decreased PELP1 driven migration/invasion in vitro, and significantly reduced in vivo metastatic potential in a preclinical model of experimental metastasis. Our results demonstrated that PELP1 binds to miR-200a and miR-141 promoters and regulates their expression by recruiting chromatin modifier HDAC2 as revealed by ChIP, siRNA and HDAC inhibitor assays. Taken together, our results suggest that PELP1 regulates tumor metastasis by controlling the expression and functions of the tumor metastasis suppressors miR-200a and miR-141.
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spelling pubmed-39359882015-01-10 Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer Roy, Sudipa Saha Gonugunta, Vijaya Kumar Bandyopadhyay, Abhik Rao, Manjeet K Goodall, Gregory J Sun, LuZhe Tekmal, Rajeshwar R Vadlamudi, Ratna K Oncogene Article Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 is a nuclear receptor coregulator that is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer patients. Here, we show that PELP1 modulates expression of metastasis-influencing microRNAs (miRs) to promote cancer metastasis. Whole genome miR array analysis using PELP1 over expressing and under expressing model cells revealed that miR-200a and miR-141 levels inversely correlated with PELP1 expression. Consistent with this, PELP1 knockdown resulted in lower expression of miR-200a target genes ZEB1 and ZEB2. PELP1 knockdown significantly reduced tumor growth and metastasis compared with parental cells in an orthotopic xenograft tumor model. Furthermore, re-introduction of miR-200a and miR-141 mimetics into PELP1 overexpressing cells reversed PELP1 target gene expression, decreased PELP1 driven migration/invasion in vitro, and significantly reduced in vivo metastatic potential in a preclinical model of experimental metastasis. Our results demonstrated that PELP1 binds to miR-200a and miR-141 promoters and regulates their expression by recruiting chromatin modifier HDAC2 as revealed by ChIP, siRNA and HDAC inhibitor assays. Taken together, our results suggest that PELP1 regulates tumor metastasis by controlling the expression and functions of the tumor metastasis suppressors miR-200a and miR-141. 2013-08-26 2014-07-10 /pmc/articles/PMC3935988/ /pubmed/23975430 http://dx.doi.org/10.1038/onc.2013.332 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
Roy, Sudipa Saha
Gonugunta, Vijaya Kumar
Bandyopadhyay, Abhik
Rao, Manjeet K
Goodall, Gregory J
Sun, LuZhe
Tekmal, Rajeshwar R
Vadlamudi, Ratna K
Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer
title Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer
title_full Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer
title_fullStr Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer
title_full_unstemmed Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer
title_short Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer
title_sort significance of pelp1/hdac2/mir-200 regulatory network in emt and metastasis of breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935988/
https://www.ncbi.nlm.nih.gov/pubmed/23975430
http://dx.doi.org/10.1038/onc.2013.332
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