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Transcriptional profile of HCC nodules and their infiltrating monocytes

ABSTRACT: Transcriptional profile of HCC nodules and their infiltrating monocytes

PROVIDER: PRJNA388872 | ENA |

REPOSITORIES: ENA

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Transcriptional profile of HCC nodules and their infiltrating monocytes

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Project description:Monocytes, macrophages and microglia make up a large part of the glioma environment and have an important role in maintaining and propagating glioma progression. Targeting these cells to inhibit their tumor promoting effect and reprogramming them into an anti-tumor phenotype has been one of the focal points of glioma therapy. In this study we have analyzed the transcriptomes of 8 different monocyte subgroups derived from the brain and the blood of glioma bearing mice. This includes the immune expression profile of blood-derived monocytes versus tumor infiltrating monocytes identifying increased expression of both pro- and anti-inflammatory pathways in tumor infiltrating monocytes. To identify new markers and targets for therapy in these different cell populations, we created a user-friendly web-based tool accessible at www.glioma-monocytes.com (temporary password 'MM2MM2'). In addition, this tool can be used for validation purposes and to elucidate gene expression profiles of tumor interacting-monocytes and macrophages as well as blood-derived circulating monocytes. Analysis of the transcriptomal profile of monocyte in a glioma mouse model Result: Infiltrating monocytes and macrophages express a high level of activation as compared to blood monocytes

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miRNA expression profiles of peripheral monocytes and glioblastoma-infiltrating macrophages

Project description:MicroRNAs (miRNAs) are non-coding molecules involved in post-transcriptional gene regulation that have been shown to modulate tumor cell proliferation and apoptosis and to act as oncogenes or tumor-suppressor genes. Although miRNAs have been linked to tumor progression, the connection between tumor-mediated immune modulation and miRNAs has yet to be explored. Specifically, how the miRNA dysregulation affects the monocyte-derived glioblastoma-infiltrating macrophages, the most abundant immune cell population within the glioblastoma microenvironment, and their immune suppressive properties has not been evaluated to date. Here we managed to purify the glioblastoma-infiltrating macrophages from the tumor microenvironment and compared their miRNA expression profile with the matched peripheral monocytes from the peripheral blood of the same GBM patient as well as with healthy donors. Of note, several most down-regulated miRNA candidates revealed in this study, including miR-142-3p, were also known for their role in mediating tumor-associated immunosuppression. These results suggest a novel approach to identify miRNA immune therapeutics using a two-step process: 1) screen miRNA expression from tumor-associated immune cells relative to normal immune cell, and 2) select and prioritize potential candidates on the basis of binding to immunosuppressive pathways or mechanisms. In the study presented here, 12 samples, including peripheral monocyte samples from 4 healthy donors, peripheral monocytes from 4 GBM patients and matched tumor-infiltrating macrophages extracted from the glioblastoma microenvironment, were used to acquire the miRNA expression profiles of 1732 unique mature miRNA sequences via the Phalanx Human miRNA OneArray Microarray v3 Platform.

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