Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma

Abstract Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and pro...

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Autores principales:	Nidhi Sharma, Shivanjali Saxena, Ishan Agrawal, Shalini Singh, Varsha Srinivasan, S. Arvind, Sridhar Epari, Sushmita Paul, Sushmita Jha
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce120f1da5894c3ba7c56e2bff4db2ab
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spelling	oai:doaj.org-article:ce120f1da5894c3ba7c56e2bff4db2ab2021-12-02T15:08:31ZDifferential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma10.1038/s41598-019-44854-42045-2322https://doaj.org/article/ce120f1da5894c3ba7c56e2bff4db2ab2019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44854-4https://doaj.org/toc/2045-2322Abstract Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and progression of several cancers. There is a dearth of reports linking NLRs and AIM2 to glioma pathology. NLRs are expressed by cells of innate immunity, including monocytes, macrophages, dendritic cells, endothelial cells, and neutrophils, as well as cells of the adaptive immune system. NLRs are critical regulators of major inflammation, cell death, immune and cancer-associated pathways. We used a data-driven approach to identify NLRs, AIM2 and NLR-associated gene expression and methylation patterns in low grade glioma and glioblastoma, using The Cancer Genome Atlas (TCGA) patient datasets. Since TCGA data is obtained from tumor tissue, comprising of multiple cell populations including glioma cells, endothelial cells and tumor-associated microglia/macrophages we have used multiple cell lines and human brain tissues to identify cell-specific effects. TCGA data mining showed significant differential NLR regulation and strong correlation with survival in different grades of glioma. We report differential expression and methylation of NLRs in glioma, followed by NLRP12 identification as a candidate prognostic marker for glioma progression. We found that Nlrp12 deficient microglia show increased colony formation while Nlrp12 deficient glioma cells show decreased cellular proliferation. Immunohistochemistry of human glioma tissue shows increased NLRP12 expression. Interestingly, microglia show reduced migration towards Nlrp12 deficient glioma cells.Nidhi SharmaShivanjali SaxenaIshan AgrawalShalini SinghVarsha SrinivasanS. ArvindSridhar EpariSushmita PaulSushmita JhaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nidhi Sharma Shivanjali Saxena Ishan Agrawal Shalini Singh Varsha Srinivasan S. Arvind Sridhar Epari Sushmita Paul Sushmita Jha Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma
description	Abstract Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and progression of several cancers. There is a dearth of reports linking NLRs and AIM2 to glioma pathology. NLRs are expressed by cells of innate immunity, including monocytes, macrophages, dendritic cells, endothelial cells, and neutrophils, as well as cells of the adaptive immune system. NLRs are critical regulators of major inflammation, cell death, immune and cancer-associated pathways. We used a data-driven approach to identify NLRs, AIM2 and NLR-associated gene expression and methylation patterns in low grade glioma and glioblastoma, using The Cancer Genome Atlas (TCGA) patient datasets. Since TCGA data is obtained from tumor tissue, comprising of multiple cell populations including glioma cells, endothelial cells and tumor-associated microglia/macrophages we have used multiple cell lines and human brain tissues to identify cell-specific effects. TCGA data mining showed significant differential NLR regulation and strong correlation with survival in different grades of glioma. We report differential expression and methylation of NLRs in glioma, followed by NLRP12 identification as a candidate prognostic marker for glioma progression. We found that Nlrp12 deficient microglia show increased colony formation while Nlrp12 deficient glioma cells show decreased cellular proliferation. Immunohistochemistry of human glioma tissue shows increased NLRP12 expression. Interestingly, microglia show reduced migration towards Nlrp12 deficient glioma cells.
format	article
author	Nidhi Sharma Shivanjali Saxena Ishan Agrawal Shalini Singh Varsha Srinivasan S. Arvind Sridhar Epari Sushmita Paul Sushmita Jha
author_facet	Nidhi Sharma Shivanjali Saxena Ishan Agrawal Shalini Singh Varsha Srinivasan S. Arvind Sridhar Epari Sushmita Paul Sushmita Jha
author_sort	Nidhi Sharma
title	Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma
title_short	Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma
title_full	Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma
title_fullStr	Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma
title_full_unstemmed	Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma
title_sort	differential expression profile of nlrs and aim2 in glioma and implications for nlrp12 in glioblastoma
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ce120f1da5894c3ba7c56e2bff4db2ab
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Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma

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