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

Abstract

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-1β and GSDMD cleavage. Rilei Jiang, Bing Lu and Fanchao Feng contributed equally to this work.

Mechanistic role of pyroptosis in tumor microenvironment and tumor immunotherapy

“…TCONS-14036, a tumor suppressive lncRNAs interferes with miR-1228-5p-mediated targeting of PRKCDBP. Importantly, PRKCDBP triggered the stimulation of NLRP3 inflammasomes and consequent activation of caspase-1-mediated cleavage of GSDMD (44). SNH suppressed NSCLC growth principally through activation of pyroptosis via TCONS-14036/miR-1228-5p/PRKCDBP pathway.…”