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Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells

BACKGROUND: Molecular profiling of colorectal cancer (CRC) based on global gene expression has revealed multiple dysregulated signalling pathways associated with drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is not fully characterised. METHODS: Bioinformatics data an...

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Autores principales: Vishnubalaji, Radhakrishnan, Yue, Shijun, Alfayez, Musaad, Kassem, Moustapha, Liu, Fei-Fei, Aldahmash, Abdullah, Alajez, Nehad M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043592/
https://www.ncbi.nlm.nih.gov/pubmed/27708551
http://dx.doi.org/10.1186/s12935-016-0355-9
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author Vishnubalaji, Radhakrishnan
Yue, Shijun
Alfayez, Musaad
Kassem, Moustapha
Liu, Fei-Fei
Aldahmash, Abdullah
Alajez, Nehad M.
author_facet Vishnubalaji, Radhakrishnan
Yue, Shijun
Alfayez, Musaad
Kassem, Moustapha
Liu, Fei-Fei
Aldahmash, Abdullah
Alajez, Nehad M.
author_sort Vishnubalaji, Radhakrishnan
collection PubMed
description BACKGROUND: Molecular profiling of colorectal cancer (CRC) based on global gene expression has revealed multiple dysregulated signalling pathways associated with drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is not fully characterised. METHODS: Bioinformatics data analysis were conducted on the GSE21510 dataset. Leniviral technology was utilized to stably express BMP2 in the HCT116 CRC model. Gene expression profiling was conducted using Agilent microarray platform while data normalization and bioinformatics were conducted using GeneSpring software. Changes in gene expression were assessed using qRT-PCR. AlamarBlue assay was used to assess cell viability in vitro. In vivo experiments were conducted using SCID mice. RESULTS: Our data revealed frequent downregulation of BMP2 in primary CRC tissues. Additionally, interrogation of publically available gene expression datasets revealed significant downregulation of BMP2 in metastatic recurrent compared to non-metastatic cancer (p = 0.02). Global gene expression analysis in CRC cells over-expressing BMP2 revealed multiple dysregulated pathways mostly affecting cell cycle and DNA damage response. Concordantly, lentiviral-mediated re-expression of BMP2 inhibited HCT116 CRC growth, sphere formation, clonogenic potential, cell migration, and sensitized CRC cells to 5-fluorouracil (5-FU) in vitro. Additionally, BMP2 inhibited CRC tumor formation in SCID mice. CONCLUSIONS: Our data revealed an inhibitory role for BMP2 in CRC, suggesting that restoration of BMP2 expression could be a potential therapeutic strategy for CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12935-016-0355-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-50435922016-10-05 Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells Vishnubalaji, Radhakrishnan Yue, Shijun Alfayez, Musaad Kassem, Moustapha Liu, Fei-Fei Aldahmash, Abdullah Alajez, Nehad M. Cancer Cell Int Primary Research BACKGROUND: Molecular profiling of colorectal cancer (CRC) based on global gene expression has revealed multiple dysregulated signalling pathways associated with drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is not fully characterised. METHODS: Bioinformatics data analysis were conducted on the GSE21510 dataset. Leniviral technology was utilized to stably express BMP2 in the HCT116 CRC model. Gene expression profiling was conducted using Agilent microarray platform while data normalization and bioinformatics were conducted using GeneSpring software. Changes in gene expression were assessed using qRT-PCR. AlamarBlue assay was used to assess cell viability in vitro. In vivo experiments were conducted using SCID mice. RESULTS: Our data revealed frequent downregulation of BMP2 in primary CRC tissues. Additionally, interrogation of publically available gene expression datasets revealed significant downregulation of BMP2 in metastatic recurrent compared to non-metastatic cancer (p = 0.02). Global gene expression analysis in CRC cells over-expressing BMP2 revealed multiple dysregulated pathways mostly affecting cell cycle and DNA damage response. Concordantly, lentiviral-mediated re-expression of BMP2 inhibited HCT116 CRC growth, sphere formation, clonogenic potential, cell migration, and sensitized CRC cells to 5-fluorouracil (5-FU) in vitro. Additionally, BMP2 inhibited CRC tumor formation in SCID mice. CONCLUSIONS: Our data revealed an inhibitory role for BMP2 in CRC, suggesting that restoration of BMP2 expression could be a potential therapeutic strategy for CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12935-016-0355-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-09-29 /pmc/articles/PMC5043592/ /pubmed/27708551 http://dx.doi.org/10.1186/s12935-016-0355-9 Text en © The Author(s) 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 Primary Research
Vishnubalaji, Radhakrishnan
Yue, Shijun
Alfayez, Musaad
Kassem, Moustapha
Liu, Fei-Fei
Aldahmash, Abdullah
Alajez, Nehad M.
Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
title Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
title_full Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
title_fullStr Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
title_full_unstemmed Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
title_short Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
title_sort bone morphogenetic protein 2 (bmp2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043592/
https://www.ncbi.nlm.nih.gov/pubmed/27708551
http://dx.doi.org/10.1186/s12935-016-0355-9
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