The sodium new houttuyfonate suppresses NSCLC via activating pyroptosis through TCONS-14036/miR-1228-5p/PRKCDBP pathway

Several studies have suggested the potential value of Houttuynia cordata as a therapeutic agent in lung cancer, but direct evidence is still lacking. The study aimed to determine the regulatory impact of a major H. cordata constituent derivative (sodium new houttuyfonate [SNH]) on lncRNA networks in non-small cell lung cancer (NSCLC) to identify new potential therapeutic targets. After exposing NSCLC cells to SNH, we analysed the following: cell death (via flow cytometry, TUNEL and ASC speck formation assays), immune factors (via ELISA), gene transcription (via RT-qPCR), subcellular localisation (via FISH), gene-gene and gene-protein interactions (via dual-luciferase reporter and RNA immunoprecipitation assays, respectively) and protein expression and distribution (via western blotting and immunocytochemistry or immunohistochemistry). In addition, statistical analysis (via one-way ANOVA or unpaired t-tests) was performed. Exposure to SNH promoted NSCLC cell pyroptosis, concomitant with significant up-regulation of TCONS-14036, a novel lncRNA. Mechanistic research demonstrated that TCONS-14036 functions as a competing endogenous (ce)RNA by sequestering microRNA (miR)-1228-5p, thereby up-regulating PRKCDBP-encoding transcript levels. Indeed, PRKCDBP promoted pyroptosis by activating the NLRP3 inflammasome, resulting in CASP1, IL-1 beta and GSDMD cleavage. Our findings elucidate the potential molecular mechanisms underlying the ability of SNH to suppress NSCLC growth through activation of pyroptosis via the TCONS-14036/miR-1228-5p/PRKCDBP pathway. Thus, we identify a new potential therapeutic targets for NSCLC.

Automated summary

The study indicated that a derivative of Houttuynia cordata (SNH) promoted pyroptosis in non-small cell lung cancer (NSCLC) cells by up-regulating a novel lncRNA (TCONS-14036) and activating the TCONS-14036/miR-1228-5p/PRKCDBP pathway. This finding offers a potential therapeutic target for NSCLC.