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LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration

BACKGROUND: lncRNAs affect adaptive and innate immunity of cancer via mediating functional states of immune cells, genes, and pathways. Nonetheless, little is known about the molecular mechanism of lncRNA-mediated CD8+ T cell immune infiltration in progression of clear cell renal cell carcinoma (ccR...

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Autores principales: Wu, Jinfeng, Lin, Rongcheng, Zhang, Lei, Wei, Yongbao, Zhang, Ruochen, Cai, Wanghai, Hu, Weilie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436564/
https://www.ncbi.nlm.nih.gov/pubmed/36060659
http://dx.doi.org/10.1155/2022/2582474
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author Wu, Jinfeng
Lin, Rongcheng
Zhang, Lei
Wei, Yongbao
Zhang, Ruochen
Cai, Wanghai
Hu, Weilie
author_facet Wu, Jinfeng
Lin, Rongcheng
Zhang, Lei
Wei, Yongbao
Zhang, Ruochen
Cai, Wanghai
Hu, Weilie
author_sort Wu, Jinfeng
collection PubMed
description BACKGROUND: lncRNAs affect adaptive and innate immunity of cancer via mediating functional states of immune cells, genes, and pathways. Nonetheless, little is known about the molecular mechanism of lncRNA-mediated CD8+ T cell immune infiltration in progression of clear cell renal cell carcinoma (ccRCC). We designed this work to investigate the role of LINC00887 in regulating CD8+ T cell immune infiltration in ccRCC. METHODS: Correlation between LINC00887 and immune factors and the expression level of LINC00887 in ccRCC were analyzed by bioinformatics methods (TCGA-KIRC database, “edgeR” package, “clusterProfiler” package, and “CIBERSORT” package). LINC00887 expression in ccRCC was examined via RT-qPCR. The cytokilling capacity of CD8+ T cells was evaluated by the lactate dehydrogenase assay. The apoptotic ability of CD8+ T cells was measured by flow cytometry. The chemotactic ability of CD8+ T cells was revealed by chemotaxis assay. CXCR3, CXCL9, and CXCL10 levels were assessed by RT-qPCR. RESULTS: As suggested by bioinformatics analysis, LINC00887 was markedly upregulated in ccRCC patients and associated with expression of immune-suppression molecule, thereby abating the immune infiltration level of CD8+ cells in tumor tissue. As revealed by cellular assay, LINC00887 was upregulated in ccRCC cells, and knockdown of LINC00887 resulted in a decreased PD-L1 expression, increased CD8+ T cell toxicity, decreased apoptotic levels, and enhanced chemotaxis. Moreover, we found that LINC00887 exhibited inhibitory effect on immune infiltration of CD8+ cells in clinical tissues. CONCLUSIONS: The results of this study suggested that LINC00887 promoted ccRCC progression by inhibiting immune infiltration of CD8+ T cells, providing new insights into pathogenesis of ccRCC and suggesting LINC00887 being a promising immunotherapy target for ccRCC.
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spelling pubmed-94365642022-09-02 LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration Wu, Jinfeng Lin, Rongcheng Zhang, Lei Wei, Yongbao Zhang, Ruochen Cai, Wanghai Hu, Weilie Comput Math Methods Med Research Article BACKGROUND: lncRNAs affect adaptive and innate immunity of cancer via mediating functional states of immune cells, genes, and pathways. Nonetheless, little is known about the molecular mechanism of lncRNA-mediated CD8+ T cell immune infiltration in progression of clear cell renal cell carcinoma (ccRCC). We designed this work to investigate the role of LINC00887 in regulating CD8+ T cell immune infiltration in ccRCC. METHODS: Correlation between LINC00887 and immune factors and the expression level of LINC00887 in ccRCC were analyzed by bioinformatics methods (TCGA-KIRC database, “edgeR” package, “clusterProfiler” package, and “CIBERSORT” package). LINC00887 expression in ccRCC was examined via RT-qPCR. The cytokilling capacity of CD8+ T cells was evaluated by the lactate dehydrogenase assay. The apoptotic ability of CD8+ T cells was measured by flow cytometry. The chemotactic ability of CD8+ T cells was revealed by chemotaxis assay. CXCR3, CXCL9, and CXCL10 levels were assessed by RT-qPCR. RESULTS: As suggested by bioinformatics analysis, LINC00887 was markedly upregulated in ccRCC patients and associated with expression of immune-suppression molecule, thereby abating the immune infiltration level of CD8+ cells in tumor tissue. As revealed by cellular assay, LINC00887 was upregulated in ccRCC cells, and knockdown of LINC00887 resulted in a decreased PD-L1 expression, increased CD8+ T cell toxicity, decreased apoptotic levels, and enhanced chemotaxis. Moreover, we found that LINC00887 exhibited inhibitory effect on immune infiltration of CD8+ cells in clinical tissues. CONCLUSIONS: The results of this study suggested that LINC00887 promoted ccRCC progression by inhibiting immune infiltration of CD8+ T cells, providing new insights into pathogenesis of ccRCC and suggesting LINC00887 being a promising immunotherapy target for ccRCC. Hindawi 2022-08-25 /pmc/articles/PMC9436564/ /pubmed/36060659 http://dx.doi.org/10.1155/2022/2582474 Text en Copyright © 2022 Jinfeng Wu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wu, Jinfeng
Lin, Rongcheng
Zhang, Lei
Wei, Yongbao
Zhang, Ruochen
Cai, Wanghai
Hu, Weilie
LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration
title LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration
title_full LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration
title_fullStr LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration
title_full_unstemmed LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration
title_short LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration
title_sort linc00887 fosters development of clear cell renal cell carcinoma via inhibiting cd8+ t cell immune infiltration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436564/
https://www.ncbi.nlm.nih.gov/pubmed/36060659
http://dx.doi.org/10.1155/2022/2582474
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