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PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing
Polypyrimidine tract-binding protein 3 (PTBP3) is an essential RNA-binding protein with roles in RNA splicing, 3′ end processing and translation. Although increasing evidence implicates PTBP3 in several cancers, its role in gastric cancer metastasis remains poorly explored. In this study, we found t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948206/ https://www.ncbi.nlm.nih.gov/pubmed/29752441 http://dx.doi.org/10.1038/s41419-018-0608-8 |
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author | Liang, Xin Chen, Weixia Shi, Haiyang Gu, Xiangyu Li, Yueqi Qi, Yingxue Xu, Ke Zhao, Aiguang Liu, Jianwen |
author_facet | Liang, Xin Chen, Weixia Shi, Haiyang Gu, Xiangyu Li, Yueqi Qi, Yingxue Xu, Ke Zhao, Aiguang Liu, Jianwen |
author_sort | Liang, Xin |
collection | PubMed |
description | Polypyrimidine tract-binding protein 3 (PTBP3) is an essential RNA-binding protein with roles in RNA splicing, 3′ end processing and translation. Although increasing evidence implicates PTBP3 in several cancers, its role in gastric cancer metastasis remains poorly explored. In this study, we found that PTBP3 was upregulated in the gastric cancer tissues of patients with lymph node metastasis. Patients with high PTBP3 expression levels had significantly shorter survival than those with low PTBP3 expression. Overexpression/knockdown of PTBP3 expression had no effect on proliferation, whereas it regulated migration and invasion in vitro. In addition, when a mouse xenotransplant model of MKN45 was established, knockdown of PTBP3 in MKN45 cells caused the formation of tumours that were smaller in size than their counterparts, with suppression of tumour lymphangiogenesis and metastasis to regional lymph nodes. Furthermore, we identified caveolin 1 (CAV1) as a downstream target of PTBP3. RNA immunoprecipitation (RIP) assays and dual-luciferase reporter gene assays indicated that PTBP3 interacted with the CU-rich region of the CAV1 gene to downregulate CAV1α expression. Knockdown of CAV1α abrogated the reduction of FAK and Src induced by PTBP3 knockdown. In summary, our findings provide experimental evidence that PTBP3 may function as a metastatic gene in gastric cancer by regulating CAV1 through alternative splicing. |
format | Online Article Text |
id | pubmed-5948206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59482062018-05-14 PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing Liang, Xin Chen, Weixia Shi, Haiyang Gu, Xiangyu Li, Yueqi Qi, Yingxue Xu, Ke Zhao, Aiguang Liu, Jianwen Cell Death Dis Article Polypyrimidine tract-binding protein 3 (PTBP3) is an essential RNA-binding protein with roles in RNA splicing, 3′ end processing and translation. Although increasing evidence implicates PTBP3 in several cancers, its role in gastric cancer metastasis remains poorly explored. In this study, we found that PTBP3 was upregulated in the gastric cancer tissues of patients with lymph node metastasis. Patients with high PTBP3 expression levels had significantly shorter survival than those with low PTBP3 expression. Overexpression/knockdown of PTBP3 expression had no effect on proliferation, whereas it regulated migration and invasion in vitro. In addition, when a mouse xenotransplant model of MKN45 was established, knockdown of PTBP3 in MKN45 cells caused the formation of tumours that were smaller in size than their counterparts, with suppression of tumour lymphangiogenesis and metastasis to regional lymph nodes. Furthermore, we identified caveolin 1 (CAV1) as a downstream target of PTBP3. RNA immunoprecipitation (RIP) assays and dual-luciferase reporter gene assays indicated that PTBP3 interacted with the CU-rich region of the CAV1 gene to downregulate CAV1α expression. Knockdown of CAV1α abrogated the reduction of FAK and Src induced by PTBP3 knockdown. In summary, our findings provide experimental evidence that PTBP3 may function as a metastatic gene in gastric cancer by regulating CAV1 through alternative splicing. Nature Publishing Group UK 2018-05-11 /pmc/articles/PMC5948206/ /pubmed/29752441 http://dx.doi.org/10.1038/s41419-018-0608-8 Text en © The Author(s) 2018 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Liang, Xin Chen, Weixia Shi, Haiyang Gu, Xiangyu Li, Yueqi Qi, Yingxue Xu, Ke Zhao, Aiguang Liu, Jianwen PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing |
title | PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing |
title_full | PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing |
title_fullStr | PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing |
title_full_unstemmed | PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing |
title_short | PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing |
title_sort | ptbp3 contributes to the metastasis of gastric cancer by mediating cav1 alternative splicing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948206/ https://www.ncbi.nlm.nih.gov/pubmed/29752441 http://dx.doi.org/10.1038/s41419-018-0608-8 |
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