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CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression

Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA i...

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Autores principales: Zhang, He, Zou, Chendan, Qiu, Zini, E, Fang, Li, Qiang, Chen, Miao, Wang, Dayong, Tan, Qinrui, Yin, Wanli, Matunda, Cedric, Wang, Hefei, Zhang, Yongjian, Zhan, Chao, Wang, Chuxuan, Wu, Yue, Xuan, Xiuchen, Wang, Yayan, Zou, Chaoxia, Lv, Guixiang, Gao, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511356/
https://www.ncbi.nlm.nih.gov/pubmed/32968053
http://dx.doi.org/10.1038/s41419-020-02984-y
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author Zhang, He
Zou, Chendan
Qiu, Zini
E, Fang
Li, Qiang
Chen, Miao
Wang, Dayong
Tan, Qinrui
Yin, Wanli
Matunda, Cedric
Wang, Hefei
Zhang, Yongjian
Zhan, Chao
Wang, Chuxuan
Wu, Yue
Xuan, Xiuchen
Wang, Yayan
Zou, Chaoxia
Lv, Guixiang
Gao, Xu
author_facet Zhang, He
Zou, Chendan
Qiu, Zini
E, Fang
Li, Qiang
Chen, Miao
Wang, Dayong
Tan, Qinrui
Yin, Wanli
Matunda, Cedric
Wang, Hefei
Zhang, Yongjian
Zhan, Chao
Wang, Chuxuan
Wu, Yue
Xuan, Xiuchen
Wang, Yayan
Zou, Chaoxia
Lv, Guixiang
Gao, Xu
author_sort Zhang, He
collection PubMed
description Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA immunoprecipitation to uncover the transcriptome-wide CPEB3-bound mRNAs (CPEB3 binder) in HCC. Bioinformatic analysis indicates that CPEB3 binders are closely related to cancer progression, especially HCC metastasis. Further studies confirmed that metadherin (MTDH) is a direct target of CPEB3. CPEB3 can suppress the translation of MTDH mRNA in vivo and in vitro. Besides, luciferase assay demonstrated that CPEB3 interacted with 3′-untranslated region of MTDH mRNA and inhibited its translation. Subsequently, CPEB3 inhibited the epithelial–mesenchymal transition and metastasis of HCC cells through post-transcriptional regulation of MTDH. In addition, cpeb3 knockout mice are more susceptible to carcinogen-induced hepatocarcinogenesis and subsequent lung metastasis. Our results also indicated that CPEB3 was a good prognosis marker, which is downregulated in HCC tissue. In conclusion, our results demonstrated that CPEB3 played an important role in HCC progression and targeting CPEB3-mediated mRNA translation might be a favorable therapeutic approach.
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spelling pubmed-75113562020-10-08 CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression Zhang, He Zou, Chendan Qiu, Zini E, Fang Li, Qiang Chen, Miao Wang, Dayong Tan, Qinrui Yin, Wanli Matunda, Cedric Wang, Hefei Zhang, Yongjian Zhan, Chao Wang, Chuxuan Wu, Yue Xuan, Xiuchen Wang, Yayan Zou, Chaoxia Lv, Guixiang Gao, Xu Cell Death Dis Article Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA immunoprecipitation to uncover the transcriptome-wide CPEB3-bound mRNAs (CPEB3 binder) in HCC. Bioinformatic analysis indicates that CPEB3 binders are closely related to cancer progression, especially HCC metastasis. Further studies confirmed that metadherin (MTDH) is a direct target of CPEB3. CPEB3 can suppress the translation of MTDH mRNA in vivo and in vitro. Besides, luciferase assay demonstrated that CPEB3 interacted with 3′-untranslated region of MTDH mRNA and inhibited its translation. Subsequently, CPEB3 inhibited the epithelial–mesenchymal transition and metastasis of HCC cells through post-transcriptional regulation of MTDH. In addition, cpeb3 knockout mice are more susceptible to carcinogen-induced hepatocarcinogenesis and subsequent lung metastasis. Our results also indicated that CPEB3 was a good prognosis marker, which is downregulated in HCC tissue. In conclusion, our results demonstrated that CPEB3 played an important role in HCC progression and targeting CPEB3-mediated mRNA translation might be a favorable therapeutic approach. Nature Publishing Group UK 2020-09-23 /pmc/articles/PMC7511356/ /pubmed/32968053 http://dx.doi.org/10.1038/s41419-020-02984-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, He
Zou, Chendan
Qiu, Zini
E, Fang
Li, Qiang
Chen, Miao
Wang, Dayong
Tan, Qinrui
Yin, Wanli
Matunda, Cedric
Wang, Hefei
Zhang, Yongjian
Zhan, Chao
Wang, Chuxuan
Wu, Yue
Xuan, Xiuchen
Wang, Yayan
Zou, Chaoxia
Lv, Guixiang
Gao, Xu
CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression
title CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression
title_full CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression
title_fullStr CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression
title_full_unstemmed CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression
title_short CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression
title_sort cpeb3-mediated mtdh mrna translational suppression restrains hepatocellular carcinoma progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511356/
https://www.ncbi.nlm.nih.gov/pubmed/32968053
http://dx.doi.org/10.1038/s41419-020-02984-y
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