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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Pyroptosis is an immunogenic form of regulated cell death mediated by NLRP3 inflammasome activation, caspase-1, and gasdermin D. Unlike apoptosis, pyroptosis promotes anti-tumor immunity through IL-1\u03b2 and IL-18 release, making it a promising therapeutic target in hepatocellular carcinoma (HCC). Although the SNHG7\/miR-34a\/SIRT1 axis has been experimentally linked to NLRP3-dependent pyroptosis, whether it functions as a systems-level regulatory module coordinating the balance between drug resistance and multiple cell-fate outcomes remains unknown. To address this question, we developed a network medicine framework using a Boolean network model integrating drug resistance, senescence, apoptosis, and pyroptosis pathways in HCC. The model was constructed from experimentally validated molecular interactions and independently validated using gain- and loss-of-function perturbation studies that were not used during model construction, demonstrating strong agreement with experimental observations. Our analysis identified a previously unreported MYC\u2013SNHG7\u2013miR-34a double-negative feedback loop, establishing miR-34a as a central regulatory hub controlling cell-fate decisions. Perturbation analysis predicted that SNHG7 inhibition shifts cells from drug resistance toward pyroptosis, identifying restoration of miR-34a activity as a potential strategy to induce immunogenic cell death. These findings provide a systems-level framework for therapeutic targeting of the MYC\u2013SNHG7\u2013miR-34a axis in HCC.<\/jats:p>","DOI":"10.3390\/ijms27198441","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MYC\u2013SNHG7\u2013miR-34a-5p Feedback Loop Orchestrates GSDMD-Dependent Pyroptosis in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3338-2799","authenticated-orcid":false,"given":"Houemakou Rimaud","family":"Djidonou","sequence":"first","affiliation":[{"name":"Bioinformatics Multidisciplinary Environment-BioME\u2014Digital Metropole Institute, Federal University of Rio Grande do Norte, Natal 59076-550, RN, Brazil"},{"name":"Children\u2019s Cancer Institute, Porto Alegre 90620-110, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5423-592X","authenticated-orcid":false,"given":"La\u00eds de Carvalho","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Bioinformatics Multidisciplinary Environment-BioME\u2014Digital Metropole Institute, Federal University of Rio Grande do Norte, Natal 59076-550, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1901-9173","authenticated-orcid":false,"given":"Djorkaeff O.","family":"Fontinele","sequence":"additional","affiliation":[{"name":"Bioinformatics Multidisciplinary Environment-BioME\u2014Digital Metropole Institute, Federal University of Rio Grande do Norte, Natal 59076-550, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-8345","authenticated-orcid":false,"given":"Daner A.","family":"Silveira","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Institute, Porto Alegre 90620-110, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-6860","authenticated-orcid":false,"given":"Marialva","family":"Sinigaglia","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Institute, Porto Alegre 90620-110, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6113-8834","authenticated-orcid":false,"given":"Joao Paulo M. 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