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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

ABSTRACT: 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

PROVIDER: PRJNA514988 | ENA |

REPOSITORIES: ENA

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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

Project description:We investigate the molecular targets and pathways that the neem extracts and the associated compounds act through, to bring about tumor suppression by using a genome-wide functional pooled shRNA screen on head and neck squamous cell carcinoma cell line treated with crude neem leaf extracts. 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 further analyzed differences in gene expression in HSC-4 cells, upon treatment with neem leaf extract in a time-dependent manner, followed by a time-dependent rescue. Our results indicate that neem extract simultaneously affects various important molecular signaling pathways in head and neck cancer cells, some (TGF-β/HSF-1) of which may be therapeutic targets for this devastating tumor.

2019-01-15 | GSE125021 | GEO

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.

Project 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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