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GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer

BACKGROUND: GLI pathogenesis-related 1 (GLIPR1) was originally identified in glioblastomas and its expression was also found to be down-regulated in prostate cancer. Functional studies revealed both growth suppression and proapoptotic activities for GLIPR1 in multiple cancer cell lines. GLIPR1’s rol...

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Autores principales: Sheng, Xiumei, Bowen, Nathan, Wang, Zhengxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797332/
https://www.ncbi.nlm.nih.gov/pubmed/26988096
http://dx.doi.org/10.1186/s12943-016-0508-4
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author Sheng, Xiumei
Bowen, Nathan
Wang, Zhengxin
author_facet Sheng, Xiumei
Bowen, Nathan
Wang, Zhengxin
author_sort Sheng, Xiumei
collection PubMed
description BACKGROUND: GLI pathogenesis-related 1 (GLIPR1) was originally identified in glioblastomas and its expression was also found to be down-regulated in prostate cancer. Functional studies revealed both growth suppression and proapoptotic activities for GLIPR1 in multiple cancer cell lines. GLIPR1’s role in lung cancer has not been investigated. Protein arginine methyltransferase 5 (PRMT5) is a protein arginine methyltransferase and forms a stoichiometric complex with the WD repeat domain 77 (WDR77) protein. Both PRMT5 and WDR77 are essential for growth of lung epithelial and cancer cells. But additional gene products that interact genetically or biochemichally with PRMT5 and WDR77 in the control of lung cancer cell growth are not characterized. METHODS: DNA microarray and immunostaining were used to detect GLIPR1 expression during lung development and lung tumorigenesis. GLIPR1 expression was also analyzed in the TCGA lung cancer cohort. The consequence of GLIPR1 on growth of lung cancer cells in the tissue culture and lung tumor xenografts in the nude mice was observed. RESULTS: We found that GLIPR1 expression is negatively associated with PRMT5/WDR77. GLIPR1 is absent in growing epithelial cells at the early stages of mouse lung development and highly expressed in the adult lung. Expression of GLIPR1 was down-regulated during lung tumorigenesis and its expression suppressed growth of lung cancer cells in the tissue culture and lung tumor xenografts in mice. GLIPR1 regulates lung cancer growth through the V-Erb-B avian erythroblastic leukemia viral oncogene homolog 3 (ErbB3). CONCLUSIONS: This study reveals a novel pathway that PRMT5/WDR77 regulates GLIPR1 expression to control lung cancer cell growth and GLIPR1 as a potential therapeutic agent for lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-016-0508-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-47973322016-03-19 GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer Sheng, Xiumei Bowen, Nathan Wang, Zhengxin Mol Cancer Research BACKGROUND: GLI pathogenesis-related 1 (GLIPR1) was originally identified in glioblastomas and its expression was also found to be down-regulated in prostate cancer. Functional studies revealed both growth suppression and proapoptotic activities for GLIPR1 in multiple cancer cell lines. GLIPR1’s role in lung cancer has not been investigated. Protein arginine methyltransferase 5 (PRMT5) is a protein arginine methyltransferase and forms a stoichiometric complex with the WD repeat domain 77 (WDR77) protein. Both PRMT5 and WDR77 are essential for growth of lung epithelial and cancer cells. But additional gene products that interact genetically or biochemichally with PRMT5 and WDR77 in the control of lung cancer cell growth are not characterized. METHODS: DNA microarray and immunostaining were used to detect GLIPR1 expression during lung development and lung tumorigenesis. GLIPR1 expression was also analyzed in the TCGA lung cancer cohort. The consequence of GLIPR1 on growth of lung cancer cells in the tissue culture and lung tumor xenografts in the nude mice was observed. RESULTS: We found that GLIPR1 expression is negatively associated with PRMT5/WDR77. GLIPR1 is absent in growing epithelial cells at the early stages of mouse lung development and highly expressed in the adult lung. Expression of GLIPR1 was down-regulated during lung tumorigenesis and its expression suppressed growth of lung cancer cells in the tissue culture and lung tumor xenografts in mice. GLIPR1 regulates lung cancer growth through the V-Erb-B avian erythroblastic leukemia viral oncogene homolog 3 (ErbB3). CONCLUSIONS: This study reveals a novel pathway that PRMT5/WDR77 regulates GLIPR1 expression to control lung cancer cell growth and GLIPR1 as a potential therapeutic agent for lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-016-0508-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-18 /pmc/articles/PMC4797332/ /pubmed/26988096 http://dx.doi.org/10.1186/s12943-016-0508-4 Text en © Sheng et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sheng, Xiumei
Bowen, Nathan
Wang, Zhengxin
GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
title GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
title_full GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
title_fullStr GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
title_full_unstemmed GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
title_short GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
title_sort gli pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797332/
https://www.ncbi.nlm.nih.gov/pubmed/26988096
http://dx.doi.org/10.1186/s12943-016-0508-4
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