Bioinformatic analysis of the influence of IL-33 on IFN-γ expression in tumor microenvironment

doi:10.3969/j.issn.1006-7795.2021.02.014

Abstract

Abstract: Objective To analyze the impact of interleukin-33 (IL-33) on tumor microenvironment by bioinformatic methods. To find the mechanism by which IL-33 upregulates interferon-gamma (IFN-γ) expression.Methods We analyzed the impact of IL-33 expression on patients' survival time by the Kaplan Meier Online analyzing tool. Data were downloaded from gene expression omnibus (GEO), which were subject to a gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We found the function and signal pathway of genes influenced by IL-33 and downloaded data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) from which we extracted the expression of IL-33 and AU-rich element binding factor 1 (AUF1) and analyzed the correlation between IL-33 and AUF1. Results Kaplan Meier Online analysis results showed that patients who expressed IL-33 at high level had a better prognosis. In the St2 (the receptor of IL-33) knockout mouse colon carcinoma model, the expression of IFN-γ significantly decreased. The genes influenced by IL-33 were mainly annotated by genes respond to interferon-gamma, genes of cellular response to interferon-gamma, genes responding to virus, genes regulating response to biotic stimulus. The data from CPTAC revealed that the expression of IL-33 and AUF1 had a significant negative correlation. Conclusion IL-33 can upregulate the expression of IFN-γ of immune cells in tumor microenvironment. IL-33 could downregulate the expression of AUF1, which belongs to AUF1- and signal transduction-regulated complex (ASTRC). AUF1 attacked mRNA whose 3'UTR have an AU-rich element (ARE). IL-33 could protect IFN-γ mRNA by downregulating AUF1.

Key words: interleukin-33, computational biology, immunotherapy, transcriptome, proteome

CLC Number:

R392.12

Han Hongju, Su Ziyang, Zhou Yujie, Wang Xi. Bioinformatic analysis of the influence of IL-33 on IFN-γ expression in tumor microenvironment[J]. Journal of Capital Medical University, 2021, 42(2): 243-250.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2021.02.014

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2021/V42/I2/243

References

[1] Qi L, Zhang Q, Miao Y, et al.Interleukin-33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development[J]. Int J Cancer, 2020, 146(5): 1421-1434.
[2] Kienzl M, Hasenoehrl C, Valadez-Cosmes P, et al.IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils[J]. Oncoimmunology, 2020, 9(1): 1776059.
[3] Xu L, Zheng Y, Wang J, et al.IL-33 activates CD8+T and NK cells through MyD88 pathway to suppress the lung cancer cell growth in mice[J]. Biotechnol Lett, 2020, 42(7): 1113-1121.
[4] Ochayon D E, Ali A, Alarcon P C, et al.IL-33 promotes type 1 cytokine expression via p38 MAPK in human NK cells[J]. J Leukoc Biol, 2020, 107(4): 663-671.
[5] Jin Z, Lei L, Lin D, et al.IL-33 released in the liver inhibits tumor growth via promotion of CD4(+) and CD8(+) T cell responses in hepatocellular carcinoma[J]. J Immunol, 2018, 201(12): 3770-3779.
[6] Eissmann M F, Dijkstra C, Wouters M A, et al.Interleukin 33 signaling restrains sporadic colon cancer in an interferon-gamma-dependent manner[J]. Cancer Immunol Res, 2018, 6(4): 409-421.
[7] Lucarini V, Ziccheddu G, Macchia I, et al.IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils[J]. Oncoimmunology, 2017, 6(6): e1317420.
[8] Sinsimer K S, Gratacos F M, Knapinska A M, et al.Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay[J]. Mol Cell Biol, 2008, 28(17): 5223-5237.
[9] Li M L, Defren J, Brewer G.Hsp27 and F-box protein beta-TrCP promote degradation of mRNA decay factor AUF1[J]. Mol Cell Biol, 2013, 33(11): 2315-2326.
[10] Knapinska A M, Gratacos F M, Krause C D, et al.Chaperone Hsp27 modulates AUF1 proteolysis and AU-rich element-mediated mRNA degradation[J]. Mol Cell Biol, 2011, 31(7): 1419-1431.
[11] J Guhaniyogi G B. Regulation of mRNA stability in mammalian cells[J]. Gene, 2001, 265(1-2): 11-23.
[12] Davila D, Jimenez-Mateos E M, Mooney C M, et al. Hsp27 binding to the 3'UTR of bim mRNA prevents neuronal death during oxidative stress-induced injury: a novel cytoprotective mechanism[J]. Mol Biol Cell, 2014, 25(21): 3413-3423.
[13] Gong P J, Shao Y C, Huang S R, et al.Hypoxia-associated prognostic markers and competing endogenous RNA co-expression networks in breast cancer[J]. Front Oncol, 2020, 10:579868.
[14] Liew F Y, Girard J P, Turnquist H R.Interleukin-33 in health and disease[J]. Nat Rev Immunol, 2016, 16(11): 676-689.
[15] Milovanovic M, Volarevic V, Radosavljevic G, et al.IL-33/ST2 axis in inflammation and immunopathology[J]. Immunol Res, 2012, 52(1-2): 89-99.
[16] Baumann C, Bonilla W V, Frohlich A, et al.T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses[J]. Proc Natl Acad Sci U S A, 2015, 112(13): 4056-4061.
[17] Komai-Koma M, Wang E, Kurowska-Stolarska M, et al.Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12[J]. Immunobiology, 2016, 221(3): 412-417.
[18] Lusty E, Poznanski S M, Kwofie K, et al.IL-18/IL-15/IL-12 synergy induces elevated and prolonged IFN-gamma production by ex vivo expanded NK cells which is not due to enhanced STAT4 activation[J]. Mol Immunol, 2017, 88:138-147.
[19] Mccarthy P C, Phair I R, Greger C, et al.IL-33 regulates cytokine production and neutrophil recruitment via the p38 MAPK-activated kinases MK2/3[J]. Immunol Cell Biol, 2019, 97(1): 54-71.
[20] Laroia G, Cuesta R, Brewer G, et al.Control of mRNA decay by heat shock-ubiquitin-proteasome pathway[J]. Science, 1999, 284(5413): 499-502.
[21] Mavropoulos A, Sully G, Cope A P, et al.Stabilization of IFN-gamma mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells[J]. Blood, 2005, 105(1): 282-288.