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Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent
microRNA regulation network is important for the cancer genetic heterogeneity. Relative to the increasing numbers of microRNA's targets identified, upstream regulatory mechanisms that control functional microRNAs are less well-documented. Here, we investigated the function of miR-31, a pleiotro...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279440/ https://www.ncbi.nlm.nih.gov/pubmed/25568668 |
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author | Ning, Zhifeng Zhu, Hua Li, Feifei Liu, Qing Liu, Gefei Tan, Tao Zhang, Bo Chen, Shaobin Li, Guanwu Huang, Dongyang Meltzer, Stephen J. Zhang, Hao |
author_facet | Ning, Zhifeng Zhu, Hua Li, Feifei Liu, Qing Liu, Gefei Tan, Tao Zhang, Bo Chen, Shaobin Li, Guanwu Huang, Dongyang Meltzer, Stephen J. Zhang, Hao |
author_sort | Ning, Zhifeng |
collection | PubMed |
description | microRNA regulation network is important for the cancer genetic heterogeneity. Relative to the increasing numbers of microRNA's targets identified, upstream regulatory mechanisms that control functional microRNAs are less well-documented. Here, we investigated the function of miR-31, a pleiotropically-acting microRNA, in esophageal squamous cell cancer (ESCC). We demonstrated that miR-31 only exerted tumor-suppressive effects in TE-7 ESCC cells, but not in TE-1 ESCC cells, although both of these cell lines harbor inactive p53. Interestingly, TE-1 cells highly expressed p21, while p21 levels were virtually undetectable in TE-7 cells, suggesting a p21-dependent mechanism of miR-31-mediated tumor suppression. Accordingly, knockdown of p21 in TE-1 cells reversed the tumor suppressive actions of miR-31. In patient ESCC specimens, real-time RT-PCR analysis revealed that expression of E2F2 and STK40, two known miR-31 target oncogenes, was negatively correlated with the expression of miR-31 in a p21-dependent manner, supporting the conclusion that miR-31 only downregulates its target oncogenes when p21 levels are low. Collectively, these data suggest a novel mechanism through which the tumor-suppressive effect of miR-31 is p21-dependent. In addition, we speculate that delivery of miR-31 could provide therapeutic benefit in the personalized management of a subgroup of ESCC patients with p21-deficient tumors. |
format | Online Article Text |
id | pubmed-4279440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-42794402015-01-07 Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent Ning, Zhifeng Zhu, Hua Li, Feifei Liu, Qing Liu, Gefei Tan, Tao Zhang, Bo Chen, Shaobin Li, Guanwu Huang, Dongyang Meltzer, Stephen J. Zhang, Hao Genes Cancer Research Paper microRNA regulation network is important for the cancer genetic heterogeneity. Relative to the increasing numbers of microRNA's targets identified, upstream regulatory mechanisms that control functional microRNAs are less well-documented. Here, we investigated the function of miR-31, a pleiotropically-acting microRNA, in esophageal squamous cell cancer (ESCC). We demonstrated that miR-31 only exerted tumor-suppressive effects in TE-7 ESCC cells, but not in TE-1 ESCC cells, although both of these cell lines harbor inactive p53. Interestingly, TE-1 cells highly expressed p21, while p21 levels were virtually undetectable in TE-7 cells, suggesting a p21-dependent mechanism of miR-31-mediated tumor suppression. Accordingly, knockdown of p21 in TE-1 cells reversed the tumor suppressive actions of miR-31. In patient ESCC specimens, real-time RT-PCR analysis revealed that expression of E2F2 and STK40, two known miR-31 target oncogenes, was negatively correlated with the expression of miR-31 in a p21-dependent manner, supporting the conclusion that miR-31 only downregulates its target oncogenes when p21 levels are low. Collectively, these data suggest a novel mechanism through which the tumor-suppressive effect of miR-31 is p21-dependent. In addition, we speculate that delivery of miR-31 could provide therapeutic benefit in the personalized management of a subgroup of ESCC patients with p21-deficient tumors. Impact Journals LLC 2014-11 /pmc/articles/PMC4279440/ /pubmed/25568668 Text en Copyright: © 2014 Ning et al. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Ning, Zhifeng Zhu, Hua Li, Feifei Liu, Qing Liu, Gefei Tan, Tao Zhang, Bo Chen, Shaobin Li, Guanwu Huang, Dongyang Meltzer, Stephen J. Zhang, Hao Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent |
title | Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent |
title_full | Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent |
title_fullStr | Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent |
title_full_unstemmed | Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent |
title_short | Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent |
title_sort | tumor suppression by mir-31 in esophageal carcinoma is p21-dependent |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279440/ https://www.ncbi.nlm.nih.gov/pubmed/25568668 |
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