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Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer
Prostate cancer is the most common cause of cancer-related deaths in men. Current practices for treatment of prostate cancer are less than satisfactory because of metastasis and recurrence, which are primarily attributed to angiogenesis. Hence, anti-angiogenesis treatment is becoming a promising new...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317958/ https://www.ncbi.nlm.nih.gov/pubmed/25283513 http://dx.doi.org/10.1111/cas.12548 |
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author | Ji, Hui Li, Yuan Jiang, Fei Wang, Xingxing Zhang, Jianping Shen, Jian Yang, Xiaojun |
author_facet | Ji, Hui Li, Yuan Jiang, Fei Wang, Xingxing Zhang, Jianping Shen, Jian Yang, Xiaojun |
author_sort | Ji, Hui |
collection | PubMed |
description | Prostate cancer is the most common cause of cancer-related deaths in men. Current practices for treatment of prostate cancer are less than satisfactory because of metastasis and recurrence, which are primarily attributed to angiogenesis. Hence, anti-angiogenesis treatment is becoming a promising new approach for prostate cancer therapy. In addition to treating acute promyelocytic leukemia, arsenic trioxide (As(2)O(3)) suppresses other solid tumors, including prostate cancer. However, the effects of As(2)O(3) on angiogenesis in prostate cancer cells, and the underlying molecular mechanisms remain unclear. In the present study, As(2)O(3) attenuated angiogenic ability through microRNA-155 (miR-155)-mediated inhibition of transforming growth factor beta (TGF-β)/SMAD signal pathway in human prostate cancer PC-3 and LNCaP cells in vitro and in vivo. Briefly, As(2)O(3) inhibited the activations/expressions of both TGFβ-induced and endogenous SMAD2/3. Furthermore, As(2)O(3) improved the expression of miR-155 via DNA-demethylation. MiR-155, which targeted the SMAD2-3′UTR, decreased the expression and function of SMAD2. Knockdown of miR-155 abolished the As(2)O(3)-induced inhibitions of the TGF-β/SMAD2 signaling, the vascular endothelial growth factor secretion and angiogenesis. Through understanding a novel mechanism whereby As(2)O(3) inhibits angiogenic potential of prostate cancer cells, our study would help in the development of As(2)O(3) as a potential chemopreventive agent when used alone or in combination with other current anticancer drugs. |
format | Online Article Text |
id | pubmed-4317958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43179582015-10-05 Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer Ji, Hui Li, Yuan Jiang, Fei Wang, Xingxing Zhang, Jianping Shen, Jian Yang, Xiaojun Cancer Sci Original Articles Prostate cancer is the most common cause of cancer-related deaths in men. Current practices for treatment of prostate cancer are less than satisfactory because of metastasis and recurrence, which are primarily attributed to angiogenesis. Hence, anti-angiogenesis treatment is becoming a promising new approach for prostate cancer therapy. In addition to treating acute promyelocytic leukemia, arsenic trioxide (As(2)O(3)) suppresses other solid tumors, including prostate cancer. However, the effects of As(2)O(3) on angiogenesis in prostate cancer cells, and the underlying molecular mechanisms remain unclear. In the present study, As(2)O(3) attenuated angiogenic ability through microRNA-155 (miR-155)-mediated inhibition of transforming growth factor beta (TGF-β)/SMAD signal pathway in human prostate cancer PC-3 and LNCaP cells in vitro and in vivo. Briefly, As(2)O(3) inhibited the activations/expressions of both TGFβ-induced and endogenous SMAD2/3. Furthermore, As(2)O(3) improved the expression of miR-155 via DNA-demethylation. MiR-155, which targeted the SMAD2-3′UTR, decreased the expression and function of SMAD2. Knockdown of miR-155 abolished the As(2)O(3)-induced inhibitions of the TGF-β/SMAD2 signaling, the vascular endothelial growth factor secretion and angiogenesis. Through understanding a novel mechanism whereby As(2)O(3) inhibits angiogenic potential of prostate cancer cells, our study would help in the development of As(2)O(3) as a potential chemopreventive agent when used alone or in combination with other current anticancer drugs. Blackwell Publishing Ltd 2014-12 2014-11-05 /pmc/articles/PMC4317958/ /pubmed/25283513 http://dx.doi.org/10.1111/cas.12548 Text en © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Ji, Hui Li, Yuan Jiang, Fei Wang, Xingxing Zhang, Jianping Shen, Jian Yang, Xiaojun Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer |
title | Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer |
title_full | Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer |
title_fullStr | Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer |
title_full_unstemmed | Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer |
title_short | Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer |
title_sort | inhibition of transforming growth factor beta/smad signal by mir-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317958/ https://www.ncbi.nlm.nih.gov/pubmed/25283513 http://dx.doi.org/10.1111/cas.12548 |
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