Sofi Shazia, Jan Nusrat, Qayoom Hina, Alkhanani Mustfa, Almilaibary Abdullah, Ahmad Mir Manzoor
Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar 190006, J&K, India.
Department of Biology, College of Science, Hafr Al Batin, University of Hafr Al-Batin, 31991, Saudi Arabia.
Saudi J Biol Sci. 2023 Sep;30(9):103774. doi: 10.1016/j.sjbs.2023.103774. Epub 2023 Aug 11.
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 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.
白细胞介素19(IL-19)是一种由单核细胞产生的细胞因子,属于IL-10家族。IL-19蛋白可刺激乳腺癌(BC)细胞中纤连蛋白(FN)的表达、组装、转移及细胞分裂。IL-19与乳腺癌发病机制相关,在BC细胞中具有自分泌作用,是包括乳腺癌在内的多种肿瘤类型预后的关键预测指标。IL-19表达增强与BC患者较差的临床结局相关,可直接促进细胞增殖和迁移,同时还为肿瘤形成提供微环境。我们研究的主要目的是检测白细胞介素-19在BC发病机制中的表达谱、功能作用及预后意义,并找出其在BC中的分子机制。在这项研究中,我们使用了各种计算方法和工具,来评估IL-19在BC中的表达谱和预后意义,并发现其在BC发病机制中的作用。与其他白细胞介素相比,IL-19在BC中高度上调。此外,其水平在临界BC患者中高度过表达,主要在21-40岁年龄组的III期患者中。BC患者体内IL-19水平升高,且IL-19表达升高与较差的总生存期(OS)相关。IL-19的KEGG分析和基因本体显示,IL-19在细胞因子活性、受体-配体活性以及JAK-STAT信号通路中显著增强。此外,IL-19与IL20RA高度相关,因为后者参与JAK-STAT信号通路。研究还表明,IL-19的上调通过包括JAK TAT信号通路在内的多种途径促进肿瘤发展并影响BC患者的临床结局。总体而言,我们的研究表明IL-19会促进肿瘤生长,除标准治疗外抑制它将大大改善BC患者的治疗反应。