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Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression
Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF- [Formula: see text] B. RKIP is severely downregulated in human malignant cancers, indicating a fun...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002422/ https://www.ncbi.nlm.nih.gov/pubmed/33802672 http://dx.doi.org/10.3390/ijms22063052 |
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author | Lai, Trang Huyen Ahmed, Mahmoud Hwang, Jin Seok Zada, Sahib Pham, Trang Minh Elashkar, Omar Kim, Deok Ryong |
author_facet | Lai, Trang Huyen Ahmed, Mahmoud Hwang, Jin Seok Zada, Sahib Pham, Trang Minh Elashkar, Omar Kim, Deok Ryong |
author_sort | Lai, Trang Huyen |
collection | PubMed |
description | Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF- [Formula: see text] B. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of RKIP gene in human cancers is not well understood. In this study, we suggested a possible transcription mechanism for the regulation of RKIP in human cancer cells. We found that Metadherin (MTDH) significantly repressed the transcriptional activity of RKIP gene. An analysis of publicly available datasets showed that the knockdown of MTDH in breast and endometrial cancer cell lines induced the expression RKIP. In addition, the results obtained from qRT-PCR and ChIP analyses showed that MTDH considerably inhibited RKIP expression. In addition, the RKIP transcript levels in MTDH-knockdown or MTDH-overexpressing MCF-7 cells were likely correlated to the protein levels, suggesting that MTDH regulates RKIP expression. In conclusion, we suggest that MTDH is a novel factor that controls the RKIP transcription, which is essential for cancer progression. |
format | Online Article Text |
id | pubmed-8002422 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80024222021-03-28 Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression Lai, Trang Huyen Ahmed, Mahmoud Hwang, Jin Seok Zada, Sahib Pham, Trang Minh Elashkar, Omar Kim, Deok Ryong Int J Mol Sci Article Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF- [Formula: see text] B. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of RKIP gene in human cancers is not well understood. In this study, we suggested a possible transcription mechanism for the regulation of RKIP in human cancer cells. We found that Metadherin (MTDH) significantly repressed the transcriptional activity of RKIP gene. An analysis of publicly available datasets showed that the knockdown of MTDH in breast and endometrial cancer cell lines induced the expression RKIP. In addition, the results obtained from qRT-PCR and ChIP analyses showed that MTDH considerably inhibited RKIP expression. In addition, the RKIP transcript levels in MTDH-knockdown or MTDH-overexpressing MCF-7 cells were likely correlated to the protein levels, suggesting that MTDH regulates RKIP expression. In conclusion, we suggest that MTDH is a novel factor that controls the RKIP transcription, which is essential for cancer progression. MDPI 2021-03-17 /pmc/articles/PMC8002422/ /pubmed/33802672 http://dx.doi.org/10.3390/ijms22063052 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lai, Trang Huyen Ahmed, Mahmoud Hwang, Jin Seok Zada, Sahib Pham, Trang Minh Elashkar, Omar Kim, Deok Ryong Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression |
title | Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression |
title_full | Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression |
title_fullStr | Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression |
title_full_unstemmed | Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression |
title_short | Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression |
title_sort | transcriptional repression of raf kinase inhibitory protein gene by metadherin during cancer progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002422/ https://www.ncbi.nlm.nih.gov/pubmed/33802672 http://dx.doi.org/10.3390/ijms22063052 |
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