Fig. 4: Roles of lncRNAs in the regulation of pyroptosis in NSCLC.
From: Targeting lncRNAs in programmed cell death as a therapeutic strategy for non-small cell lung cancer
Pyroptosis can be induced via the caspase-1-dependent canonical pathway and caspase-4,5 (for human)- or caspase-11 (for mouse)-mediated non-canonical pathway. In terms of the canonical pathway, damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs) activate the inflammasome sensors NLRP3, which then recruit the effector pro-caspase-1 with the aid of the adaptor protein ASC to assemble inflammasomes, leading to the conversion of pro-caspase-1 into active caspase-1. Activation of NLRP3 inflammasome requires the involvement of the TLR4-mediated NF-κB pathway, which promotes the expression of NLRP3, pro-caspase-1, pro-IL-1β and pro-IL-18 proteins. Activated caspase-1 cleaves gasdermin D (GSDMD) and ultimately mediates pyroptosis. Besides, caspase-1 promotes the maturation of pro-inflammatory cytokines IL-1β and IL-18 by cleaving their precursor proteins, which trigger wide-ranging inflammatory responses. In the non-canonical pathway, human caspase-4 and -5 or their murine homologue caspase-11 can be directly activated by binding to lipopolysaccharide (LPS) and cleave GSDMD with efficiency similar to that of caspase-1, thereby inducing cell pyroptosis. Oncogenic lncRNAs (red font, high expression in NSCLC) participate in lung cancer-associated pyroptosis by regulating pyroptosis-related proteins.
