Department of Immunology, National Institute for Research and Development in Biomedical Pathology and Biomedical Sciences "Victor Babes", Bucharest 050096, Romania.
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Bucharest 050095, Romania.
J Immunol Res. 2020 Sep 19;2020:2549763. doi: 10.1155/2020/2549763. eCollection 2020.
Over the past decade, it has been well established that tumorigenesis is affected by chronic inflammation. During this event, proinflammatory cytokines are produced by numerous types of cells, such as fibroblasts, endothelial cells, macrophages, and tumor cells, and are able to promote the initiation, progression, and metastasis of different types of cancer. When persistent inflammation occurs, activation of inflammasome complexes is initiated, leading to its assembly and further activation of caspase, production of proinflammatory cytokines, and pyroptosis induction. The function of this multiprotein complex is not only to reassure inflammation and to promote cell death, through caspase activity, but also has been identified to have significant contributions during tumorigenesis and cancer development. So far, many efforts have been made in order to extend the knowledge of inflammasome implications and how its components could be targeted as therapeutic agents. Additionally, microRNAs (miRNAs), evolutionary conserved noncoding molecules, have emerged as pivotal players during numerous biological events by regulating gene and protein expression. Therefore, dysregulations of miRNA expressions have been correlated with inflammation during tumor development. In this review, we aim to highlight the dual role of inflammasomes and proinflammatory cytokines during carcinogenesis paired with the distinguished effects of miRNAs upon inflammation cascades during tumor growth and progression.
在过去的十年中,慢性炎症会影响肿瘤发生这一观点已经得到了充分证实。在此过程中,许多类型的细胞(如成纤维细胞、内皮细胞、巨噬细胞和肿瘤细胞)会产生促炎细胞因子,并能够促进不同类型癌症的发生、发展和转移。当持续发生炎症时,炎症小体复合物被激活,导致其组装和半胱天冬酶的进一步激活、促炎细胞因子的产生以及细胞焦亡的诱导。该多蛋白复合物的功能不仅在于通过半胱天冬酶活性来确保炎症和促进细胞死亡,而且还被确定在肿瘤发生和癌症发展中具有重要作用。迄今为止,人们已经做出了许多努力来扩展对炎症小体影响及其成分如何作为治疗剂靶向的认识。此外,microRNAs(miRNAs)是进化上保守的非编码分子,通过调节基因和蛋白质表达,在许多生物学事件中成为关键参与者。因此,miRNA 表达的失调与肿瘤发展过程中的炎症有关。在这篇综述中,我们旨在强调炎症小体和促炎细胞因子在致癌作用中的双重作用,并结合 miRNA 对肿瘤生长和进展过程中炎症级联反应的独特作用。