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The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation
Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXI...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209196/ https://www.ncbi.nlm.nih.gov/pubmed/37225681 http://dx.doi.org/10.1038/s41419-023-05862-5 |
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author | Li, Jiaying Pei, Miaomiao Xiao, Wushuang Liu, Xuehua Hong, Linjie Yu, Zhen Peng, Ying Zhang, Jieming Yang, Ping Lin, Jianjiao Wu, Xiaosheng Lin, Zhizhao Tang, Weimei Zhi, Fachao Li, Guoxin Xiang, Li Li, Aimin Liu, Side Chen, Ye Wang, Jide |
author_facet | Li, Jiaying Pei, Miaomiao Xiao, Wushuang Liu, Xuehua Hong, Linjie Yu, Zhen Peng, Ying Zhang, Jieming Yang, Ping Lin, Jianjiao Wu, Xiaosheng Lin, Zhizhao Tang, Weimei Zhi, Fachao Li, Guoxin Xiang, Li Li, Aimin Liu, Side Chen, Ye Wang, Jide |
author_sort | Li, Jiaying |
collection | PubMed |
description | Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXIP1-AS1 was transcriptionally repressed by homeobox D9 (HOXD9) and was significantly downregulated in GC tissues and cells. Decreased expression of PAXIP1-AS1 was positively correlated with tumour progression, while PAXIP1-AS1 overexpression inhibited cell growth and metastasis both in vitro and in vivo. PAXIP1-AS1 overexpression significantly attenuated HOXD9-enhanced epithelial-to-mesenchymal transition (EMT), invasion and metastasis in GC cells. Poly(A)-binding protein cytoplasmic 1 (PABPC1), an RNA-binding protein, was found to enhance the stability of PAK1 mRNA, leading to EMT progress and GC metastasis. PAXIP1-AS1 was found to directly bind to and destabilise PABPC1, thereby regulating EMT and metastasis of GC cells. In summary, PAXIP1-AS1 suppressed metastasis, and the HOXD9/PAXIP1-AS1/PABPC1/PAK1 signalling axis may be involved in the progression of GC. |
format | Online Article Text |
id | pubmed-10209196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102091962023-05-26 The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation Li, Jiaying Pei, Miaomiao Xiao, Wushuang Liu, Xuehua Hong, Linjie Yu, Zhen Peng, Ying Zhang, Jieming Yang, Ping Lin, Jianjiao Wu, Xiaosheng Lin, Zhizhao Tang, Weimei Zhi, Fachao Li, Guoxin Xiang, Li Li, Aimin Liu, Side Chen, Ye Wang, Jide Cell Death Dis Article Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXIP1-AS1 was transcriptionally repressed by homeobox D9 (HOXD9) and was significantly downregulated in GC tissues and cells. Decreased expression of PAXIP1-AS1 was positively correlated with tumour progression, while PAXIP1-AS1 overexpression inhibited cell growth and metastasis both in vitro and in vivo. PAXIP1-AS1 overexpression significantly attenuated HOXD9-enhanced epithelial-to-mesenchymal transition (EMT), invasion and metastasis in GC cells. Poly(A)-binding protein cytoplasmic 1 (PABPC1), an RNA-binding protein, was found to enhance the stability of PAK1 mRNA, leading to EMT progress and GC metastasis. PAXIP1-AS1 was found to directly bind to and destabilise PABPC1, thereby regulating EMT and metastasis of GC cells. In summary, PAXIP1-AS1 suppressed metastasis, and the HOXD9/PAXIP1-AS1/PABPC1/PAK1 signalling axis may be involved in the progression of GC. Nature Publishing Group UK 2023-05-24 /pmc/articles/PMC10209196/ /pubmed/37225681 http://dx.doi.org/10.1038/s41419-023-05862-5 Text en © The Author(s) 2023 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 Li, Jiaying Pei, Miaomiao Xiao, Wushuang Liu, Xuehua Hong, Linjie Yu, Zhen Peng, Ying Zhang, Jieming Yang, Ping Lin, Jianjiao Wu, Xiaosheng Lin, Zhizhao Tang, Weimei Zhi, Fachao Li, Guoxin Xiang, Li Li, Aimin Liu, Side Chen, Ye Wang, Jide The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation |
title | The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation |
title_full | The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation |
title_fullStr | The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation |
title_full_unstemmed | The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation |
title_short | The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation |
title_sort | hoxd9-mediated paxip1-as1 regulates gastric cancer progression through pabpc1/pak1 modulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209196/ https://www.ncbi.nlm.nih.gov/pubmed/37225681 http://dx.doi.org/10.1038/s41419-023-05862-5 |
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