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Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression
BACKGROUND: TAp63 is known as the most potent transcription activator and tumor suppressor. microRNAs (miRNAs) are increasingly recognized as essential components of the p63 pathway, mediating downstream post-transcriptional gene repression. The aim of present study was to investigate a negative fee...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349978/ https://www.ncbi.nlm.nih.gov/pubmed/27894087 http://dx.doi.org/10.18632/oncotarget.13515 |
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author | Dai, Jing Wu, Hao Zhang, Yi Gao, Kai Hu, Gui guo, Yihang Lin, Changwei Li, Xiaorong |
author_facet | Dai, Jing Wu, Hao Zhang, Yi Gao, Kai Hu, Gui guo, Yihang Lin, Changwei Li, Xiaorong |
author_sort | Dai, Jing |
collection | PubMed |
description | BACKGROUND: TAp63 is known as the most potent transcription activator and tumor suppressor. microRNAs (miRNAs) are increasingly recognized as essential components of the p63 pathway, mediating downstream post-transcriptional gene repression. The aim of present study was to investigate a negative feedback loop between TAp63 and miR-133b. RESULTS: Overexpression of TAp63 inhibited HCT-116 cell proliferation, apoptosis and invasion via miR-133b. Accordingly, miR-133b inhibited TAp63 expression through RhoA and its downstream pathways. Moreover, we demonstrated that TAp63/miR-133b could inhibit colorectal cancer proliferation and metastasis in vivo and vitro. MATERIALS AND METHODS: We evaluated the correlation between TAp63 and miR-133b in HCT-116 cells and investigated the roles of the TAp63/miR-133b feedback loop in cell proliferation, apoptosis and metastasis via MTT, flow cytometry, Transwell, and nude mouse xenograft experiments. The expression of TAp63, miR-133b, RhoA, α-tubulin and Akt was assessed via qRT-PCR, western blot and immunofluorescence analyses. miR-133b target genes were identified through luciferase reporter assays. CONCLUSIONS: miR-133b plays an important role in the anti-tumor effects of TAp63 in colorectal cancer. miR-133b may represent a tiemolecule between TAp63 and RhoA, forming a TAp63/miR-133b/RhoA negative feedback loop, which could significantly inhibit proliferation, apoptosis and metastasis. |
format | Online Article Text |
id | pubmed-5349978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53499782017-04-06 Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression Dai, Jing Wu, Hao Zhang, Yi Gao, Kai Hu, Gui guo, Yihang Lin, Changwei Li, Xiaorong Oncotarget Research Paper BACKGROUND: TAp63 is known as the most potent transcription activator and tumor suppressor. microRNAs (miRNAs) are increasingly recognized as essential components of the p63 pathway, mediating downstream post-transcriptional gene repression. The aim of present study was to investigate a negative feedback loop between TAp63 and miR-133b. RESULTS: Overexpression of TAp63 inhibited HCT-116 cell proliferation, apoptosis and invasion via miR-133b. Accordingly, miR-133b inhibited TAp63 expression through RhoA and its downstream pathways. Moreover, we demonstrated that TAp63/miR-133b could inhibit colorectal cancer proliferation and metastasis in vivo and vitro. MATERIALS AND METHODS: We evaluated the correlation between TAp63 and miR-133b in HCT-116 cells and investigated the roles of the TAp63/miR-133b feedback loop in cell proliferation, apoptosis and metastasis via MTT, flow cytometry, Transwell, and nude mouse xenograft experiments. The expression of TAp63, miR-133b, RhoA, α-tubulin and Akt was assessed via qRT-PCR, western blot and immunofluorescence analyses. miR-133b target genes were identified through luciferase reporter assays. CONCLUSIONS: miR-133b plays an important role in the anti-tumor effects of TAp63 in colorectal cancer. miR-133b may represent a tiemolecule between TAp63 and RhoA, forming a TAp63/miR-133b/RhoA negative feedback loop, which could significantly inhibit proliferation, apoptosis and metastasis. Impact Journals LLC 2016-11-23 /pmc/articles/PMC5349978/ /pubmed/27894087 http://dx.doi.org/10.18632/oncotarget.13515 Text en Copyright: © 2016 Dai et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Dai, Jing Wu, Hao Zhang, Yi Gao, Kai Hu, Gui guo, Yihang Lin, Changwei Li, Xiaorong Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression |
title | Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression |
title_full | Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression |
title_fullStr | Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression |
title_full_unstemmed | Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression |
title_short | Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression |
title_sort | negative feedback between tap63 and mir-133b mediates colorectal cancer suppression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349978/ https://www.ncbi.nlm.nih.gov/pubmed/27894087 http://dx.doi.org/10.18632/oncotarget.13515 |
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