Abstract
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.
Highlights
Inflammation represents an immune response of the host to damaging stimulation, realized by pathogens or irritants
The NLRP6 pathway is a less well-characterized mechanism, but its involvement in development and progression of colitis has been established. This may lead to the initiation of tumorigenesis, as a result of abnormal secretion of IL-18 by intestinal epithelial cells [40]. This type of inflammasome needs to be further studied in detail, but so far, it is known that NLRP6 complex influences IL-18 and goblet cell mucus secretion [41], regulates NF-κB and the mitogen-activated protein kinase (MAPK) signaling pathways [42], and controls the production of interferons type I and III [43]
The fact that IL-1β is inducing the production of protumorigenic molecules is a central event during cancer progression. Another important link between IL-1β and a protumorigenic element has come to light. It seems that the production of IL-22 is dependent on the activation of NLRP3 inflammasome with the result of IL-1β secretion from both myeloid and T cells [87]
Summary
Inflammation represents an immune response of the host to damaging stimulation, realized by pathogens or irritants. The most studied cytokine is interleukin- (IL-) 1β, which is secreted by various types of cells, such as monocytes, macrophages, fibroblasts, or endothelial cells [3] in different pathological conditions (inflammation, infection, invasion, tissue damage, or cancer) [6]. Another cause of cytokine and chemokine secretion (IL-1β and IL-18) is represented by caspase-1 activation due to conformational modifications caused by the inflammasome complex [7]. The role of inflammasome complexes is to mediate the process of host defense [16]; any alteration that occurs in the activation mechanism of the complex may lead to initiation of tumorigenesis, the appearance of autoimmune diseases, neurodegenerative diseases, or metabolic disorders [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
