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Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma

Tumor suppression by the extracts of Azadirachta indica (neem) works via anti-proliferation, cell cycle arrest, and apoptosis, demonstrated previously using cancer cell lines and live animal models. However, very little is known about the molecular targets and pathways that neem extracts and their a...

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Autores principales: Krishnan, Neeraja M., Katoh, Hiroto, Palve, Vinayak, Pareek, Manisha, Sato, Reiko, Ishikawa, Shumpei, Panda, Binay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398373/
https://www.ncbi.nlm.nih.gov/pubmed/30842898
http://dx.doi.org/10.7717/peerj.6464
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author Krishnan, Neeraja M.
Katoh, Hiroto
Palve, Vinayak
Pareek, Manisha
Sato, Reiko
Ishikawa, Shumpei
Panda, Binay
author_facet Krishnan, Neeraja M.
Katoh, Hiroto
Palve, Vinayak
Pareek, Manisha
Sato, Reiko
Ishikawa, Shumpei
Panda, Binay
author_sort Krishnan, Neeraja M.
collection PubMed
description Tumor suppression by the extracts of Azadirachta indica (neem) works via anti-proliferation, cell cycle arrest, and apoptosis, demonstrated previously using cancer cell lines and live animal models. However, very little is known about the molecular targets and pathways that neem extracts and their associated compounds act through. Here, we address this using a genome-wide functional pooled shRNA screen on head and neck squamous cell carcinoma cell lines treated with crude neem leaf extracts, known for their anti-tumorigenic activity. We analyzed differences in global clonal sizes of the shRNA-infected cells cultured under no treatment and treatment with neem leaf extract conditions, assayed using next-generation sequencing. We found 225 genes affected the cancer cell growth in the shRNA-infected cells treated with neem extract. Pathway enrichment analyses of whole-genome gene expression data from cells temporally treated with neem extract revealed important roles played by the TGF-β pathway and HSF-1-related gene network. Our results indicate that neem extract affects various important molecular signaling pathways in head and neck cancer cells, some of which may be therapeutic targets for this devastating tumor.
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spelling pubmed-63983732019-03-06 Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma Krishnan, Neeraja M. Katoh, Hiroto Palve, Vinayak Pareek, Manisha Sato, Reiko Ishikawa, Shumpei Panda, Binay PeerJ Bioinformatics Tumor suppression by the extracts of Azadirachta indica (neem) works via anti-proliferation, cell cycle arrest, and apoptosis, demonstrated previously using cancer cell lines and live animal models. However, very little is known about the molecular targets and pathways that neem extracts and their associated compounds act through. Here, we address this using a genome-wide functional pooled shRNA screen on head and neck squamous cell carcinoma cell lines treated with crude neem leaf extracts, known for their anti-tumorigenic activity. We analyzed differences in global clonal sizes of the shRNA-infected cells cultured under no treatment and treatment with neem leaf extract conditions, assayed using next-generation sequencing. We found 225 genes affected the cancer cell growth in the shRNA-infected cells treated with neem extract. Pathway enrichment analyses of whole-genome gene expression data from cells temporally treated with neem extract revealed important roles played by the TGF-β pathway and HSF-1-related gene network. Our results indicate that neem extract affects various important molecular signaling pathways in head and neck cancer cells, some of which may be therapeutic targets for this devastating tumor. PeerJ Inc. 2019-03-01 /pmc/articles/PMC6398373/ /pubmed/30842898 http://dx.doi.org/10.7717/peerj.6464 Text en ©2019 Krishnan et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Krishnan, Neeraja M.
Katoh, Hiroto
Palve, Vinayak
Pareek, Manisha
Sato, Reiko
Ishikawa, Shumpei
Panda, Binay
Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma
title Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma
title_full Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma
title_fullStr Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma
title_full_unstemmed Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma
title_short Functional genomics screen with pooled shRNA library and gene expression profiling with extracts of Azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma
title_sort functional genomics screen with pooled shrna library and gene expression profiling with extracts of azadirachta indica identify potential pathways for therapeutic targets in head and neck squamous cell carcinoma
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398373/
https://www.ncbi.nlm.nih.gov/pubmed/30842898
http://dx.doi.org/10.7717/peerj.6464
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