Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA923244 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR23063395_1.fastq.gz | Fastqsanger.gz | |||
| SRR23063395_2.fastq.gz | Fastqsanger.gz | |||
| SRR23063396_1.fastq.gz | Fastqsanger.gz | |||
| SRR23063396_2.fastq.gz | Fastqsanger.gz |
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Project description:Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.
2023-10-26 | GSE222703 | GEO
Project description:Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.
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Project description:Severe angiopathy is a major driver for diabetes associated secondary complications. Knowledge on underlying mechanisms essential for advanced therapies to attenuate these pathologies is limited. Injection of ABCB5+ stromal precursors (SPs) at the edge of non-healing diabetic wounds in a murine db/db model, closely mirroring human type II diabetes, profoundly accelerates wound closure. Strikingly, enhanced angiogenesis was substantially enforced by the release of the ribonuclease angiogenin from ABCB5+ SPs. This compensates for the profoundly reduced angiogenin expression in non-treated murine and human chronic diabetic wounds. Silencing of angiogenin in ABCB5+ SPs prior to injection significantly reduced angiogenesis, reduced numbers of M2 macrophages and delayed wound closure in diabetic db/db mice implying an unprecedented key role for angiogenin in tissue regeneration in diabetes. These data hold significant promise for further refining SPs-based therapies of non-healing diabetic foot ulcers and other pathologies with impaired angiogenesis.
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Project description:Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive subtype of kidney cancer, often associated with metastasis and recurrence. Identifying key genes involved in ccRCC progression is critical for improving treatment strategies and patient outcomes. Methods: We performed a large-scale genome-wide CRISPR screening to identify genes crucial to ccRCC progression using the DepMap database. For discovery and validation, we integrated multi-omics data from The Cancer Genome Atlas (TCGA), GEO, and the NJMU-ccRCC clinical cohort. Bioinformatics analyses, including differential expression, pathway enrichment, and protein-protein interaction network analysis, were conducted to elucidate the biological functions. To validate our findings, we employed immunohistochemistry, qRT-PCR, and various cellular assays to investigate the role of PRC1 in ccRCC. Results: CRISPR screening identified PRC1 as a key gene significantly overexpressed in ccRCC tissues from the DepMap database. Elevated PRC1 expression was associated with poor overall survival, disease-specific survival, and progression-free interval. Silencing PRC1 in ccRCC cell lines inhibited cell proliferation, migration, and colony formation. Functional enrichment analyses revealed that PRC1 is involved in essential processes such as cell cycle regulation, mitosis, and cytokinesis. Additionally, PRC1 expression was correlated with the activation of the Wnt/β-catenin pathway, suggesting that PRC1 plays a pivotal role in tumor progression. Conclusion: PRC1 emerges as a promising biomarker and therapeutic target for ccRCC. Elevated PRC1 expression is associated with poor prognosis, and its inhibition suppresses ccRCC cell proliferation and migration. Our findings underscore the crucial role of PRC1 in ccRCC progression and highlight the need for further investigation into its molecular mechanisms and therapeutic potential.
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Project description:Human Angiogenin (hAng) is a member of the ribonuclease A superfamily and a potent inducer of neovascularization. Herein, protein interactions of hAng in the nucleus and cytoplasm of the human umbilical vein cell line EA.hy926, have been investigated by mass spectroscopy. The first gel-free analysis of hAng immunoprecipitates from the cytoplasmic and nuclear extracts from EA.hy926 cancer human cell line, revealed many statistically significant potential hAng-interacting proteins. The majority of the proteins identified by the mass spectrometry analysis are parts of multiprotein complexes, and some of them are common in nucleus and cytoplasm, including spliceosome, proteasome, and molecular chaperone TRiC/CCT. These complexes are involved in crucial biological pathways, implicating thus the key role of hAng in many vital cellular processes.
2017-08-11 | PXD006583 | Pride
Project description:Human Angiogenin (hAng) is a member of the ribonuclease A superfamily and a potent inducer of neovascularization. Herein, protein interactions of hAng in the nucleus and cytoplasm of the human umbilical vein cell line EA.hy926, have been investigated by mass spectroscopy. The first gel-free analysis of hAng immunoprecipitates from the cytoplasmic and nuclear extracts from EA.hy926 cancer human cell line, revealed many statistically significant potential hAng-interacting proteins. The majority of the proteins identified by the mass spectrometry analysis are parts of multiprotein complexes, and some of them are common in nucleus and cytoplasm, including spliceosome, proteasome, and molecular chaperone TRiC/CCT. These complexes are involved in crucial biological pathways, implicating thus the key role of hAng in many vital cellular processes.
2017-08-11 | PXD006584 | Pride
Project description:To identify tRNA fragments regulated by angiogenin (ANG, Rnase 5), we sequenced 15-50nt small RNAs upon ANG overexpression and ANG knockout.
2019-10-01 | GSE130764 | GEO
Project description:Comparative analysis of cell-cell communication at single-cell resolution
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Project description:Severe angiopathy has been postulated as a major driver for diabetes associated secondary complications. So far the knowledge on underlying mechanisms and thereon based therapeutic options to attenuate these pathologies are limited. Here we systematically administered ABCB5+ MSCs for the treatment of chronic non-healing diabetic wounds employing db/db mice, a type II diabetes model as their number markedly declined during diabetes. We found that administration of ABCB5+ MSCs markedly accelerates wound closure in diabetic db/db mice as opposed to the vehicle treated control group. Strikingly, administration of ABCB5+ MSCs at the edges of the diabetic wounds triggered considerable neoangiogenesis, most likely by the releasing a Ribonuclease angiogenin that was identified through secretome analysis of ABCB5+ MSCs. Interestingly, silencing of angiogenin in ABCB5+ MSCs significantly delayed wound closure in diabetic db/db mice indicating its key role in skin regeneration. Moreover, angiogenin also impacted the polarization of macrophages. The findings from this study will provide novel insight into the unique capacity of ABCB5+ MSCs to mount an adaptive response at the wound site with the delivery of angiogenic molecules holds significant promise for the therapy of non-healing diabetes foot ulcers, and other pathologies with impaired angiogenesis. The benefits for refined stem cell based therapies is virtually unlimited.
2020-01-24 | GSE144169 | GEO
Project description:We quantified differential microRNA (miRNA) expression in Human umbilical vein endothelial cells （HUVECs）response to Angiogenin (ANG) treatment.These data were used to determine which miRNAs are altered on ANG in Human umbilical vein endothelial cells.
2016-12-13 | GSE92256 | GEO