Search

The Gasdermin protein is a membrane disruptor that can mediate immunogenic pyroptosis and elicit anti‐tumor immune function. However, cancer cells downregulate Gasdermin and develop membrane repair mechanisms to resist pyroptosis. Therefore, an artificial membrane disruptor (AMD) that can directly mediate membrane rupture in pyroptosis‐deficient cells and induce antitumor immune responses in a controllable manner will be valuable in preclinical and clinical research. A micron‐scale Ce6‐based AMD that can directly induce plasma membrane rupture (PMR) in gasdermin‐deficient tumor cells is established. Micron‐scale AMDs localize Ce6 specifically to the plasma membrane without labeling other organelles. Compared to free Ce6 molecules, the use of AMDs results in a higher degree of specificity for the plasma membrane. Due to this specificity, AMDs mediate fast and irreversible PMR under 660 nm red light. Furthermore, the AMDs are capable of inducing programmed cell death and lytic cell death in a catalytic manner, demonstrating that the amount of Ce6 used by AMDs is only one‐fifth of that used by Ce6 alone when inducing 80% of cancer cell death. In vivo, the AMDs show specificity for tumor targeting and penetration, suggesting that light‐driven programmed cell death is specific to tumors. AMDs are applied to antitumor therapy in gasdermin‐deficient tumors, resulting in efficient tumor elimination with minimal damage to major organs when combined with anti‐PD‐1 therapy. Tumor regression is correlated with PMR‐mediated inflammation and T‐cell‐based immune responses. This study provides new insights for designing bioinspired membrane disruptors for PMR and mediating anti‐tumor immunotherapy. Additionally, AMD is a dependable tool for examining the immunogenicity of PMR both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are considered as regulators of gene expression in cancers. However, cancer profiling has little focused on noncoding genes. Here, we reported that RP11–115N4.1 (here renamed novel lncRNA inhibiting proliferation and metastasis [NLIPMT]) was downregulated in breast cancer tissues. Ectopic expression of NLIPMT inhibited mammary cell proliferation, motility in vitro. Moreover, lnc‐NLIPMT reduced the growth of implanted MDA‐MB‐231 cells in vivo. Mechanistically, glycogen synthase kinase 3β (GSK3β) was identified as an effector protein regulated by lnc‐NLIPMT. Inhibition of GSK3β activity restored NLIPMT‐induced inhibition of proliferation and motility in breast cancer cells. These data reveal that lnc‐NLIPMT functions as a driver of breast cancer progression and might serve as a potential target for antimetastatic therapies. A novel long noncoding RNA was found to inhibit mammary cell proliferation and motility. Inhibition of glycogen synthase kinase 3β (GSK3β) activity restored novel lncRNA inhibiting proliferation and metastasis‐induced repression. [ABSTRACT FROM AUTHOR]