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-<inline-formula>κ<math xmlns="http://www.w3.org/1998/Math/MathML" display="...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/6/3052 |
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| author | Trang Huyen Lai Mahmoud Ahmed Jin Seok Hwang Sahib Zada Trang Minh Pham Omar Elashkar Deok Ryong Kim |
| author_facet | Trang Huyen Lai Mahmoud Ahmed Jin Seok Hwang Sahib Zada Trang Minh Pham Omar Elashkar Deok Ryong Kim |
| author_sort | Trang Huyen Lai |
| collection | DOAJ |
| 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-<inline-formula>κ<math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">κ</mi></semantics></math></inline-formula>B. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of <i>RKIP</i> 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 <i>RKIP</i> gene. An analysis of publicly available datasets showed that the knockdown of <i>MTDH</i> 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 <i>MTDH</i>-knockdown or <i>MTDH</i>-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. |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-03-10T13:10:31Z |
| publishDate | 2021-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8ef7d0384e0e41ccb7d0ad0c1a98f5ec2023-11-21T10:48:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01226305210.3390/ijms22063052Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer ProgressionTrang Huyen Lai0Mahmoud Ahmed1Jin Seok Hwang2Sahib Zada3Trang Minh Pham4Omar Elashkar5Deok Ryong Kim6Department of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, KoreaDepartment of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, KoreaDepartment of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, KoreaDepartment of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, KoreaDepartment of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, KoreaDepartment of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, KoreaDepartment of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, KoreaRaf 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-<inline-formula>κ<math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">κ</mi></semantics></math></inline-formula>B. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of <i>RKIP</i> 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 <i>RKIP</i> gene. An analysis of publicly available datasets showed that the knockdown of <i>MTDH</i> 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 <i>MTDH</i>-knockdown or <i>MTDH</i>-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.https://www.mdpi.com/1422-0067/22/6/3052RKIP/PEBP1MTDH/AEG-1VEZF1transcription factorRKIP expressionChIP assay |
| spellingShingle | Trang Huyen Lai Mahmoud Ahmed Jin Seok Hwang Sahib Zada Trang Minh Pham Omar Elashkar Deok Ryong Kim Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression International Journal of Molecular Sciences RKIP/PEBP1 MTDH/AEG-1 VEZF1 transcription factor RKIP expression ChIP assay |
| 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 | RKIP/PEBP1 MTDH/AEG-1 VEZF1 transcription factor RKIP expression ChIP assay |
| url | https://www.mdpi.com/1422-0067/22/6/3052 |
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