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Micro-RNA-632 down regulates DNAJB6 in breast cancer
DNAJB6 is a constitutively expressed member of the HSP40 family. It has been described as a negative regulator of breast tumor progression and a regulator of epithelial phenotype. Expression of DNAJB6 is reported to be compromised with tumor progression. However, factors responsible for its down-reg...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660857/ https://www.ncbi.nlm.nih.gov/pubmed/22710984 http://dx.doi.org/10.1038/labinvest.2012.87 |
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author | Mitra, Aparna Rostas, Jack W. Dyess, Donna L. Shevde, Lalita A. Samant, Rajeev S. |
author_facet | Mitra, Aparna Rostas, Jack W. Dyess, Donna L. Shevde, Lalita A. Samant, Rajeev S. |
author_sort | Mitra, Aparna |
collection | PubMed |
description | DNAJB6 is a constitutively expressed member of the HSP40 family. It has been described as a negative regulator of breast tumor progression and a regulator of epithelial phenotype. Expression of DNAJB6 is reported to be compromised with tumor progression. However, factors responsible for its down-regulation are still undefined. We used a knowledge-based screen for identifying miRNAs capable of targeting DNAJB6. In this work, we present our findings that hsa-miR-632 (miR-632) targets the coding region of DNAJB6. Invasive and metastatic breast cancer cells express high levels of miR-632 compared to mammary epithelial cells. Analysis of RNA from breast tumor specimens reveals inverse expression patterns of DNAJB6 transcript and miR-632. In response to exogenous miR-632 expression, DNAJB6 protein levels are down regulated and the resultant cell population shows significantly increased invasive ability. Silencing endogenous miR-632 abrogates invasive ability of breast cancer cells and promotes epithelial like characteristics noted by E-cadherin expression with concomitant decrease in mesenchymal markers such as Zeb2 and Slug. Thus, miR-632 is a potentially important epigenetic regulator of DNAJB6 which contributes to the down regulation of DNAJB6 and plays a supportive role in malignant progression. |
format | Online Article Text |
id | pubmed-3660857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-36608572013-05-22 Micro-RNA-632 down regulates DNAJB6 in breast cancer Mitra, Aparna Rostas, Jack W. Dyess, Donna L. Shevde, Lalita A. Samant, Rajeev S. Lab Invest Article DNAJB6 is a constitutively expressed member of the HSP40 family. It has been described as a negative regulator of breast tumor progression and a regulator of epithelial phenotype. Expression of DNAJB6 is reported to be compromised with tumor progression. However, factors responsible for its down-regulation are still undefined. We used a knowledge-based screen for identifying miRNAs capable of targeting DNAJB6. In this work, we present our findings that hsa-miR-632 (miR-632) targets the coding region of DNAJB6. Invasive and metastatic breast cancer cells express high levels of miR-632 compared to mammary epithelial cells. Analysis of RNA from breast tumor specimens reveals inverse expression patterns of DNAJB6 transcript and miR-632. In response to exogenous miR-632 expression, DNAJB6 protein levels are down regulated and the resultant cell population shows significantly increased invasive ability. Silencing endogenous miR-632 abrogates invasive ability of breast cancer cells and promotes epithelial like characteristics noted by E-cadherin expression with concomitant decrease in mesenchymal markers such as Zeb2 and Slug. Thus, miR-632 is a potentially important epigenetic regulator of DNAJB6 which contributes to the down regulation of DNAJB6 and plays a supportive role in malignant progression. 2012-06-18 2012-09 /pmc/articles/PMC3660857/ /pubmed/22710984 http://dx.doi.org/10.1038/labinvest.2012.87 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 Mitra, Aparna Rostas, Jack W. Dyess, Donna L. Shevde, Lalita A. Samant, Rajeev S. Micro-RNA-632 down regulates DNAJB6 in breast cancer |
title | Micro-RNA-632 down regulates DNAJB6 in breast cancer |
title_full | Micro-RNA-632 down regulates DNAJB6 in breast cancer |
title_fullStr | Micro-RNA-632 down regulates DNAJB6 in breast cancer |
title_full_unstemmed | Micro-RNA-632 down regulates DNAJB6 in breast cancer |
title_short | Micro-RNA-632 down regulates DNAJB6 in breast cancer |
title_sort | micro-rna-632 down regulates dnajb6 in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660857/ https://www.ncbi.nlm.nih.gov/pubmed/22710984 http://dx.doi.org/10.1038/labinvest.2012.87 |
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