Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
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
_version_ 1783648540497543168
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
work_keys_str_mv AT yangshikun epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT jiangwei epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT yangwenjie epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT yangchao epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT yangxinchen epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT chenkeyan epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT huyuanchang epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT shengefenqiang epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT luling epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT chengfeng epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT zhangfeng epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT raojianhua epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway
AT wangxuehao epigeneticallymodulatedmir1224suppressestheproliferationofhccthroughcrebmediatedactivationofyapsignalingpathway