Transcription factor MAFK binds to circRPPH to regulate SIRT gene-mediated cellular pyroptosis and lung adenocarcinoma progression

•Circ_000585 is overexpressed in LUAD and is associated with poor prognosis;•CircRPPH1 knockdown inhibits LUAD cell growth and promotes pyroptosis.•CircRPPH1 binds to MAFK to promote SIRT1 transcription;•CircRPPH1 knockdown inhibits SIRT1 level;•Overexpression of MAFK or SIRT1 impairs the effect of sh-circRPPH1 on LUAD. Lung adenocarcinoma (LUAD) represents the most prevalent subtype of lung cancer (LC), accounting for 50% of all LC cases, with its occurrence continuing to rise. Multiple pyroptotic pathway mediators are implicated in LC initiation. The study delved into the mechanism of circRPPH1 in pyroptosis in LUAD. We first examined the relationship between circRPPH1 and the clinical features of LUAD patients by analyzing circRNA gene expression profiles from the GEO database and validating findings with clinical samples. Downstream pathways influenced by circRPPH1 were identified and assessed for their roles in LUAD cell growth and pyroptosis using gain-and-loss-of-function assays. circRPPH1 was significantly upregulated in LUAD and associated with poor prognosis. It binds to the transcription factor MAFK, enhancing SIRT1 expression and activating the MAFK-Keap1 signaling pathway. Reducing circRPPH1 expression decreased SIRT1 levels, inhibited cell proliferation both in vivo and ex vivo, and increased markers of cellular pyroptosis. Additionally, overexpressing SIRT1 mitigated the effects of circRPPH1 silencing. circRPPH1 promotes LUAD progression by binding to MAFK, enhancing SIRT1 expression, and inhibiting cellular pyroptosis.