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PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis
Previous studies have demonstrated the in vitro oncogenic role of protein arginine methyltransferase 5 (PRMT5) in gastric cancer cell lines. The in vivo function of PRMT5 in gastric tumorigenesis, however, is still unexplored. Here, we showed that Prmt5 deletion in mouse gastric epithelium resulted...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295066/ https://www.ncbi.nlm.nih.gov/pubmed/35864961 http://dx.doi.org/10.7150/ijbs.71581 |
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author | Tang, Yuling Dong, Lei Zhang, Chong Li, Xiubin Li, Rongyu Lin, Huisang Qi, Yini Tang, Mingchuan Peng, Yanli Liu, Chuan Zhou, Jian Hou, Ning Liu, Wenjia Yang, Guan Yang, Xiao Teng, Yan |
author_facet | Tang, Yuling Dong, Lei Zhang, Chong Li, Xiubin Li, Rongyu Lin, Huisang Qi, Yini Tang, Mingchuan Peng, Yanli Liu, Chuan Zhou, Jian Hou, Ning Liu, Wenjia Yang, Guan Yang, Xiao Teng, Yan |
author_sort | Tang, Yuling |
collection | PubMed |
description | Previous studies have demonstrated the in vitro oncogenic role of protein arginine methyltransferase 5 (PRMT5) in gastric cancer cell lines. The in vivo function of PRMT5 in gastric tumorigenesis, however, is still unexplored. Here, we showed that Prmt5 deletion in mouse gastric epithelium resulted in spontaneous tumorigenesis in gastric antrum. All Prmt5-deficient mice displayed intestinal-type gastric cancer within 4 months of age. Of note, 20% (2/10) of Prmt5 mutants finally developed into invasive gastric cancer by 8 months of age. Gastric cancer caused by PRMT5 loss exhibited the increase in Lgr5(+) stem cells, which are proposed to contribute to both the gastric tumorigenesis and progression in mouse models. Consistent with the notion that Lgr5 is the target of Wnt/β-catenin signaling, whose activation is the most predominant driver for gastric tumorigenesis, Prmt5 mutant gastric cancer showed the activation of Wnt/β-Catenin signaling. Furthermore, in human gastric cancer samples, PRMT5 deletion and downregulation were frequently observed and associated with the poor prognosis. We propose that as opposed to the tumor-promoting role of PRMT5 well-established in the progression of various cancer types, PRMT5 functions as a tumor suppressor in vivo, at least during gastric tumor formation. |
format | Online Article Text |
id | pubmed-9295066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-92950662022-07-20 PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis Tang, Yuling Dong, Lei Zhang, Chong Li, Xiubin Li, Rongyu Lin, Huisang Qi, Yini Tang, Mingchuan Peng, Yanli Liu, Chuan Zhou, Jian Hou, Ning Liu, Wenjia Yang, Guan Yang, Xiao Teng, Yan Int J Biol Sci Research Paper Previous studies have demonstrated the in vitro oncogenic role of protein arginine methyltransferase 5 (PRMT5) in gastric cancer cell lines. The in vivo function of PRMT5 in gastric tumorigenesis, however, is still unexplored. Here, we showed that Prmt5 deletion in mouse gastric epithelium resulted in spontaneous tumorigenesis in gastric antrum. All Prmt5-deficient mice displayed intestinal-type gastric cancer within 4 months of age. Of note, 20% (2/10) of Prmt5 mutants finally developed into invasive gastric cancer by 8 months of age. Gastric cancer caused by PRMT5 loss exhibited the increase in Lgr5(+) stem cells, which are proposed to contribute to both the gastric tumorigenesis and progression in mouse models. Consistent with the notion that Lgr5 is the target of Wnt/β-catenin signaling, whose activation is the most predominant driver for gastric tumorigenesis, Prmt5 mutant gastric cancer showed the activation of Wnt/β-Catenin signaling. Furthermore, in human gastric cancer samples, PRMT5 deletion and downregulation were frequently observed and associated with the poor prognosis. We propose that as opposed to the tumor-promoting role of PRMT5 well-established in the progression of various cancer types, PRMT5 functions as a tumor suppressor in vivo, at least during gastric tumor formation. Ivyspring International Publisher 2022-07-04 /pmc/articles/PMC9295066/ /pubmed/35864961 http://dx.doi.org/10.7150/ijbs.71581 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Tang, Yuling Dong, Lei Zhang, Chong Li, Xiubin Li, Rongyu Lin, Huisang Qi, Yini Tang, Mingchuan Peng, Yanli Liu, Chuan Zhou, Jian Hou, Ning Liu, Wenjia Yang, Guan Yang, Xiao Teng, Yan PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis |
title | PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis |
title_full | PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis |
title_fullStr | PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis |
title_full_unstemmed | PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis |
title_short | PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis |
title_sort | prmt5 acts as a tumor suppressor by inhibiting wnt/β-catenin signaling in murine gastric tumorigenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295066/ https://www.ncbi.nlm.nih.gov/pubmed/35864961 http://dx.doi.org/10.7150/ijbs.71581 |
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