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Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway
Mounting evidence has demonstrated that microRNA-1224 (miR-1224) is commonly downregulated and serves as a tumor suppressor in multiple malignancies. However, the role and mechanisms responsible for miR-1224 in hepatocellular carcinoma (HCC) remain unclear. In this study, we found that the expressio...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868928/ https://www.ncbi.nlm.nih.gov/pubmed/33614242 http://dx.doi.org/10.1016/j.omtn.2021.01.008 |
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author | Yang, Shikun Jiang, Wei Yang, Wenjie Yang, Chao Yang, Xinchen Chen, Keyan Hu, Yuanchang Shen, Gefenqiang Lu, Ling Cheng, Feng Zhang, Feng Rao, Jianhua Wang, Xuehao |
author_facet | Yang, Shikun Jiang, Wei Yang, Wenjie Yang, Chao Yang, Xinchen Chen, Keyan Hu, Yuanchang Shen, Gefenqiang Lu, Ling Cheng, Feng Zhang, Feng Rao, Jianhua Wang, Xuehao |
author_sort | Yang, Shikun |
collection | PubMed |
description | Mounting evidence has demonstrated that microRNA-1224 (miR-1224) is commonly downregulated and serves as a tumor suppressor in multiple malignancies. However, the role and mechanisms responsible for miR-1224 in hepatocellular carcinoma (HCC) remain unclear. In this study, we found that the expression of miR-1224 was downregulated in HCC. Low miR-1224 expression was associated with poor clinicopathologic features and short overall survival. Moreover, the methylation status of putative CpG islands was also found to be an important part in the modulation of miR-1224 expression. miR-1224 could induce HCC cells to arrest in G0/G1 phase and inhibited the proliferation of HCC cells both in vitro and in vivo. Mechanistic investigation showed that by binding with cyclic AMP (cAMP)-response element binding protein (CREB) miR-1224 could repress the transcription and the activation of Yes-associated protein (YAP) signaling pathway. Furthermore, the expression of miR-1224 was inhibited by CREB through EZH2-mediated histone 3 lysine 27 (H3K27me3) on miR-1224 promoter, thus forming a positive feedback circuit. Our findings identify a miR-1224/CREB feedback loop for HCC progression and that blocking this circuit may represent a promising target for HCC treatment. |
format | Online Article Text |
id | pubmed-7868928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-78689282021-02-19 Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway Yang, Shikun Jiang, Wei Yang, Wenjie Yang, Chao Yang, Xinchen Chen, Keyan Hu, Yuanchang Shen, Gefenqiang Lu, Ling Cheng, Feng Zhang, Feng Rao, Jianhua Wang, Xuehao Mol Ther Nucleic Acids Original Article Mounting evidence has demonstrated that microRNA-1224 (miR-1224) is commonly downregulated and serves as a tumor suppressor in multiple malignancies. However, the role and mechanisms responsible for miR-1224 in hepatocellular carcinoma (HCC) remain unclear. In this study, we found that the expression of miR-1224 was downregulated in HCC. Low miR-1224 expression was associated with poor clinicopathologic features and short overall survival. Moreover, the methylation status of putative CpG islands was also found to be an important part in the modulation of miR-1224 expression. miR-1224 could induce HCC cells to arrest in G0/G1 phase and inhibited the proliferation of HCC cells both in vitro and in vivo. Mechanistic investigation showed that by binding with cyclic AMP (cAMP)-response element binding protein (CREB) miR-1224 could repress the transcription and the activation of Yes-associated protein (YAP) signaling pathway. Furthermore, the expression of miR-1224 was inhibited by CREB through EZH2-mediated histone 3 lysine 27 (H3K27me3) on miR-1224 promoter, thus forming a positive feedback circuit. Our findings identify a miR-1224/CREB feedback loop for HCC progression and that blocking this circuit may represent a promising target for HCC treatment. American Society of Gene & Cell Therapy 2021-01-16 /pmc/articles/PMC7868928/ /pubmed/33614242 http://dx.doi.org/10.1016/j.omtn.2021.01.008 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Yang, Shikun Jiang, Wei Yang, Wenjie Yang, Chao Yang, Xinchen Chen, Keyan Hu, Yuanchang Shen, Gefenqiang Lu, Ling Cheng, Feng Zhang, Feng Rao, Jianhua Wang, Xuehao Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway |
title | Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway |
title_full | Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway |
title_fullStr | Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway |
title_full_unstemmed | Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway |
title_short | Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway |
title_sort | epigenetically modulated mir-1224 suppresses the proliferation of hcc through creb-mediated activation of yap signaling pathway |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868928/ https://www.ncbi.nlm.nih.gov/pubmed/33614242 http://dx.doi.org/10.1016/j.omtn.2021.01.008 |
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