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MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway
Gallbladder cancer (GBC) is a leading cause of cancer-related deaths worldwide, and its prognosis remains poor, with a 5-year survival rate of ~5%. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of the metastasis-associated miRNA mi...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344207/ https://www.ncbi.nlm.nih.gov/pubmed/28060377 http://dx.doi.org/10.1038/cdd.2016.146 |
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author | Shu, Yi-Jun Bao, Run-Fa Jiang, Lin Wang, Zheng Wang, Xu-An Zhang, Fei Liang, Han-Bin Li, Huai-Feng Ye, Yuan-Yuan Xiang, Shan-Shan Weng, Hao Wu, Xiang-Song Li, Mao-Lan Hu, Yun-Ping Lu, Wei Zhang, Yi-Jian Zhu, Jian Dong, Ping Liu, Ying-Bin |
author_facet | Shu, Yi-Jun Bao, Run-Fa Jiang, Lin Wang, Zheng Wang, Xu-An Zhang, Fei Liang, Han-Bin Li, Huai-Feng Ye, Yuan-Yuan Xiang, Shan-Shan Weng, Hao Wu, Xiang-Song Li, Mao-Lan Hu, Yun-Ping Lu, Wei Zhang, Yi-Jian Zhu, Jian Dong, Ping Liu, Ying-Bin |
author_sort | Shu, Yi-Jun |
collection | PubMed |
description | Gallbladder cancer (GBC) is a leading cause of cancer-related deaths worldwide, and its prognosis remains poor, with a 5-year survival rate of ~5%. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of the metastasis-associated miRNA miR-29c-5p in GBC.We validated that expression of miR-29c-5p was significantly downregulated in GBC and was closely associated with lymph node metastasis, overall survival and disease-free survival in 40 GBC patients who were followed clinically. Ectopic overexpression of miR-29c-5p dramatically repressed proliferation, metastasis, and colony formation and induced apoptosis in vitro, and it suppressed tumorigenicity in vivo through the MAPK pathway. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) was identified as a critical effector target of miR-29c-5p. Enforced expression of miR-29c-5p significantly inhibited the expression of CPEB4, and restoration of CPEB4 expression reversed the inhibitory effects of miR-29c-5p on GBC cell proliferation and metastasis. Transforming growth factor-β (TGF-β) upregulated CPEB4 by downregulating miR-29c-5p, leading to MAPK pathway activation. In conclusion, the TGF-β/miR-29c-5p/CPEB4 axis has a pivotal role in the pathogenesis and poor prognosis of GBC, suggesting that miR-29c-5p is a tumor-suppressive miRNA that may serve as potential prognostic biomarker or therapeutic target for GBC. |
format | Online Article Text |
id | pubmed-5344207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53442072017-03-21 MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway Shu, Yi-Jun Bao, Run-Fa Jiang, Lin Wang, Zheng Wang, Xu-An Zhang, Fei Liang, Han-Bin Li, Huai-Feng Ye, Yuan-Yuan Xiang, Shan-Shan Weng, Hao Wu, Xiang-Song Li, Mao-Lan Hu, Yun-Ping Lu, Wei Zhang, Yi-Jian Zhu, Jian Dong, Ping Liu, Ying-Bin Cell Death Differ Original Paper Gallbladder cancer (GBC) is a leading cause of cancer-related deaths worldwide, and its prognosis remains poor, with a 5-year survival rate of ~5%. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of the metastasis-associated miRNA miR-29c-5p in GBC.We validated that expression of miR-29c-5p was significantly downregulated in GBC and was closely associated with lymph node metastasis, overall survival and disease-free survival in 40 GBC patients who were followed clinically. Ectopic overexpression of miR-29c-5p dramatically repressed proliferation, metastasis, and colony formation and induced apoptosis in vitro, and it suppressed tumorigenicity in vivo through the MAPK pathway. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) was identified as a critical effector target of miR-29c-5p. Enforced expression of miR-29c-5p significantly inhibited the expression of CPEB4, and restoration of CPEB4 expression reversed the inhibitory effects of miR-29c-5p on GBC cell proliferation and metastasis. Transforming growth factor-β (TGF-β) upregulated CPEB4 by downregulating miR-29c-5p, leading to MAPK pathway activation. In conclusion, the TGF-β/miR-29c-5p/CPEB4 axis has a pivotal role in the pathogenesis and poor prognosis of GBC, suggesting that miR-29c-5p is a tumor-suppressive miRNA that may serve as potential prognostic biomarker or therapeutic target for GBC. Nature Publishing Group 2017-03 2017-01-06 /pmc/articles/PMC5344207/ /pubmed/28060377 http://dx.doi.org/10.1038/cdd.2016.146 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Original Paper Shu, Yi-Jun Bao, Run-Fa Jiang, Lin Wang, Zheng Wang, Xu-An Zhang, Fei Liang, Han-Bin Li, Huai-Feng Ye, Yuan-Yuan Xiang, Shan-Shan Weng, Hao Wu, Xiang-Song Li, Mao-Lan Hu, Yun-Ping Lu, Wei Zhang, Yi-Jian Zhu, Jian Dong, Ping Liu, Ying-Bin MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway |
title | MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway |
title_full | MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway |
title_fullStr | MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway |
title_full_unstemmed | MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway |
title_short | MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK pathway |
title_sort | microrna-29c-5p suppresses gallbladder carcinoma progression by directly targeting cpeb4 and inhibiting the mapk pathway |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344207/ https://www.ncbi.nlm.nih.gov/pubmed/28060377 http://dx.doi.org/10.1038/cdd.2016.146 |
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