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MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer
TGFBR2 serves as an initial regulator of the TGF-β signaling pathway, and loss or reduction of its expression leads to uncontrolled cell growth and invasion. TGFBR2 plays a crucial role in the carcinogenesis and malignant process of gastric cancer, but the mechanism remains unclear. In this study, w...
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/PMC5078094/ https://www.ncbi.nlm.nih.gov/pubmed/27120811 http://dx.doi.org/10.18632/oncotarget.8946 |
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author | Qu, Yanjun Zhang, Haiyang Duan, Jingjing Liu, Rui Deng, Ting Bai, Ming Huang, Dingzhi Li, Hongli Ning, Tao Zhang, Le Wang, Xia Ge, Shaohua Zhou, Likun Zhong, Benfu Ying, Guoguang Ba, Yi |
author_facet | Qu, Yanjun Zhang, Haiyang Duan, Jingjing Liu, Rui Deng, Ting Bai, Ming Huang, Dingzhi Li, Hongli Ning, Tao Zhang, Le Wang, Xia Ge, Shaohua Zhou, Likun Zhong, Benfu Ying, Guoguang Ba, Yi |
author_sort | Qu, Yanjun |
collection | PubMed |
description | TGFBR2 serves as an initial regulator of the TGF-β signaling pathway, and loss or reduction of its expression leads to uncontrolled cell growth and invasion. TGFBR2 plays a crucial role in the carcinogenesis and malignant process of gastric cancer, but the mechanism remains unclear. In this study, we found that TGFBR2 protein levels were consistently upregulated in gastric cancer tissues, whereas TGFBR2 mRNA levels varied among these tissues, indicating that a post-transcriptional mechanism is involved in the regulation of TGFBR2. MiRNAs are known to regulate gene expression at the post-transcriptional level. Therefore, we performed bioinformatics analyses to search for miRNAs potentially targeting TGFBR2. MiR-17-5p was found to bind to the 3′UTR of TGFBR2 mRNA, and further validation of this specific binding was performed through a reporter assay. An inverse correlation between miR-17-5p and TGFBR2 protein was observed in gastric cancer tissues. Cell studies revealed that miR-17-5p negatively regulated TGFBR2 expression by directly binding to the 3′UTR of TGFBR2 mRNA, thereby promoting cell growth and migration. We also validated the role of TGFBR2 using siRNA and an overexpression plasmid. The results of our study suggest a novel regulatory network in gastric cancer mediated by miR-17-5p and TGFBR2 and may indicate that TGFBR2 could serve as a new therapeutic target in gastric cancer. |
format | Online Article Text |
id | pubmed-5078094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50780942016-10-28 MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer Qu, Yanjun Zhang, Haiyang Duan, Jingjing Liu, Rui Deng, Ting Bai, Ming Huang, Dingzhi Li, Hongli Ning, Tao Zhang, Le Wang, Xia Ge, Shaohua Zhou, Likun Zhong, Benfu Ying, Guoguang Ba, Yi Oncotarget Research Paper TGFBR2 serves as an initial regulator of the TGF-β signaling pathway, and loss or reduction of its expression leads to uncontrolled cell growth and invasion. TGFBR2 plays a crucial role in the carcinogenesis and malignant process of gastric cancer, but the mechanism remains unclear. In this study, we found that TGFBR2 protein levels were consistently upregulated in gastric cancer tissues, whereas TGFBR2 mRNA levels varied among these tissues, indicating that a post-transcriptional mechanism is involved in the regulation of TGFBR2. MiRNAs are known to regulate gene expression at the post-transcriptional level. Therefore, we performed bioinformatics analyses to search for miRNAs potentially targeting TGFBR2. MiR-17-5p was found to bind to the 3′UTR of TGFBR2 mRNA, and further validation of this specific binding was performed through a reporter assay. An inverse correlation between miR-17-5p and TGFBR2 protein was observed in gastric cancer tissues. Cell studies revealed that miR-17-5p negatively regulated TGFBR2 expression by directly binding to the 3′UTR of TGFBR2 mRNA, thereby promoting cell growth and migration. We also validated the role of TGFBR2 using siRNA and an overexpression plasmid. The results of our study suggest a novel regulatory network in gastric cancer mediated by miR-17-5p and TGFBR2 and may indicate that TGFBR2 could serve as a new therapeutic target in gastric cancer. Impact Journals LLC 2016-04-23 /pmc/articles/PMC5078094/ /pubmed/27120811 http://dx.doi.org/10.18632/oncotarget.8946 Text en Copyright: © 2016 Qu et al. http://creativecommons.org/licenses/by/2.5/ 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 Qu, Yanjun Zhang, Haiyang Duan, Jingjing Liu, Rui Deng, Ting Bai, Ming Huang, Dingzhi Li, Hongli Ning, Tao Zhang, Le Wang, Xia Ge, Shaohua Zhou, Likun Zhong, Benfu Ying, Guoguang Ba, Yi MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer |
title | MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer |
title_full | MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer |
title_fullStr | MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer |
title_full_unstemmed | MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer |
title_short | MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer |
title_sort | mir-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078094/ https://www.ncbi.nlm.nih.gov/pubmed/27120811 http://dx.doi.org/10.18632/oncotarget.8946 |
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