Elucidation of interleukin-19 as a therapeutic target for breast cancer by computational analysis and experimental validation |
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Institution: | 1. Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar 190006, J&K, India;2. Department of Biology, College of Science, Hafr Al Batin, University of Hafr Al-Batin, 31991, Saudi Arabia;3. Department of Family and Community Medicine, Faculty of Medicine, Al Baha University, Albaha 65511, Saudi Arabia |
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Abstract: | Interleukin 19 (IL-19) is a cytokine produced by monocytes and belongs to the family of IL-10. The IL-19 protein stimulates fibronectin (FN) expression and assembly, metastasis, and cell division in breast cancer (BC) cells. IL-19, which is connected to breast pathogenesis and has an autocrine action in BC cells, is a key predictor of prognosis for many tumour forms, including breast cancer. Augmented IL-19 expression has been related to poorer clinical outcomes for patients with BC and directly enhances proliferation and migration while also serving as a microenvironment for tumour formation. The main aim of our study was to examine the expression profile, functional role, and prognostic significance of interleukin-19 in BC pathogenesis and also to find out the molecular mechanism of IL-19 in BC. In this work, we used the various computational approach and tools, to evaluate the expression profile and prognostic implication of IL-19 in BC and discover the role of IL-19 in BC pathogenesis. IL-19 was shown to be highly upregulated in BC as compared to other interleukins. Also, its levels were highly overexpressed in liminal BC patients, mostly in 3rd stage groups under the age group of 21–40 years. IL-19 levels were increased in BC and elevated expression of IL-19 was examined to have worse overall survival (OS). The KEGG analysis and gene ontology of IL-19 depict that IL-19 is significantly augmented in cytokine activity and receptor-ligand activity and also in the JAK-STAT signaling pathway. Moreover, IL-19 showed a high correlation with IL20RA, as later is involved with the JAK-STAT signaling pathway. The in-vivo and in-vitro studies have also reflected that upregulation of IL-19 enhances tumor development and affects clinical outcomes in BC patients through several pathways including the JAK TAT signalling pathway. Overall, our study indicates that IL-19 increases tumour growth and that inhibiting it in addition to standard treatments will greatly improve BC patient’s therapeutic responses. |
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Keywords: | Upregulation Prognosis Breast cancer Gene ontology Overall survival Pathogenesis BC"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"Breast cancer KEGG"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"Kyoto Encyclopedia of Genes and Genomes IL"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"Interleukin TME"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"Tumor microenvironment TGF-β"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"Transforming growth factor-β IFNs"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"Interferons HR"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"Hazard ratio GO"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"Gene ontology MMP"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"Matrix Metalloproteinase BP"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"Biological process IL20RA"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"Interleukin 20 Receptor Subunit Alpha TNF"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"Tumor necrosis factor OS"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"Overall survival MF"} {"#name":"keyword" "$":{"id":"k0170"} "$$":[{"#name":"text" "_":"Molecular function NF-к β"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"Nuclear Factor-Kappa beta |
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