The role of NLRP3 inflammasome in hepatocellular carcinoma

Abstract

Inflammasomes play an important role in innate immunity. As a signal platform, they deal with the excessive pathogenic products and cellular products related to stress and injury. So far, the best studied and most characteristic inflammasome is the NLR-family pyrin domain-containing protein 3(NLRP3) inflammasome, which is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. The formation of NLRP3 inflammasome complexes results in the activation of caspase-1, the maturation of interleukin (IL)-1β and IL-18, and pyroptosis. Many studies have demonstrated that NLRP3 inflammasome not only participates in tumorigenesis, but also plays a protective role in some cancers. Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Currently, due to the lack of effective treatment methods for HCC, the therapeutic effect of HCC has not been ideal. Therefore, it is particularly urgent to explore the pathogenesis of HCC and find its effective treatment methods. The increasing evidences indicate that NLRP3 inflammasome plays a vital role in HCC, however, the related mechanisms are not fully understood. Hence, we focused on the recent progress about the role of NLRP3 inflammasome in HCC, and analyzed the relevant mechanisms in detail to provide reference for the future in-depth researches.

Noncoding RNAs and programmed cell death in hepatocellular carcinoma: Significant role of epigenetic modifications in prognosis, chemoresistance, and tumor recurrence rate

“…These molecular changes occur by external agents, like unhealthy nutrition, viral infection, and alcohol taking (Kouroumalis et al, 2023). In addition to the mentioned causes, cell cycle defect, aberrant DNA methylation, microRNA (miRNA) impairment, immune regulation disruption, oxidative stress, and epithelial-to-mesenchymal cell transformation (EMT) (Zhao et al, 2023). Cell cycle defect is one of the key markers of tumor development.…”

“…The role of many oncomicroRNAs, including miR-1246, miR-19a-3p, and miR-376c-3p, in the formation of HCC tumor by inhibiting RORα expression and affecting SOX6 and the Wnt/β-catenin signaling pathway, has also been illustrated (Ruiz-Manriquez et al, 2022). The activity of several immune agents, like tumor-associated neutrophils (TANs), cancer-associated fibroblasts (CAFs), and inflammasome (Kotsari et al, 2023;Zhao et al, 2023). TANs and CAFs are linked with tumor growth and lymph node metastasis in different solid human tumors, like HCC (Kotsari et al, 2023).…”

“…TANs and CAFs are linked with tumor growth and lymph node metastasis in different solid human tumors, like HCC (Kotsari et al, 2023). NLRP3 inflammasome potentiates HCC through upregulation of caspase-1-assocated pyroptosis of malignant cells (Zhao et al, 2023). Oxidative stress also serves an important role in HCC progression by regulating the expression of growth factors and cytokines involved in cancer cell viability.…”

MASLD and aspartame: are new studies in the horizon?

“…NLRP3 inflammasome initiation is linked with the onset of liver cancer, particularly HCC (16). New clinical trials should target NLRP3 inflammasome activation and compounds that may be able to act on it (17).…”