MYC-SNHG7-miR-34a-5p Feedback Loop Orchestrates GSDMD-Dependent Pyroptosis in Hepatocellular Carcinoma.
4 affiliations
- 1Bioinformatics Multidisciplinary Environment-BioME-Digital Metropole Institute, Federal University of Rio Grande do Norte, Natal 59076-550, RN, Brazil.
- 2Children's Cancer Institute, Porto Alegre 90620-110, RS, Brazil.
- 3Department of Biochemistry, Federal University of Rio Grande do Norte, Natal 59076-550, RN, Brazil.
- 4Departamento de Física, Universidade Federal de Santa Maria, Santa Maria 97105-900, RS, Brazil.
Abstract
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-1β 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-SNHG7-miR-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-SNHG7-miR-34a axis in HCC.
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BibTeX
@article{djidonou2026mycsnhg7mir34a5p,
title = {{MYC-SNHG7-miR-34a-5p Feedback Loop Orchestrates GSDMD-Dependent Pyroptosis in Hepatocellular Carcinoma.}},
author = {Houemakou Rimaud Djidonou and Laís de Carvalho Gonçalves and Djorkaeff O Fontinele and Daner A Silveira and Marialva Sinigaglia and Joao Paulo M S Lima and José Carlos M Mombach and Shantanu Gupta},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198441},
url = {https://europepmc.org/article/MED/42883693},
note = {CC BY},
}
RIS
TY - JOUR
TI - MYC-SNHG7-miR-34a-5p Feedback Loop Orchestrates GSDMD-Dependent Pyroptosis in Hepatocellular Carcinoma.
AU - Houemakou Rimaud Djidonou
AU - Laís de Carvalho Gonçalves
AU - Djorkaeff O Fontinele
AU - Daner A Silveira
AU - Marialva Sinigaglia
AU - Joao Paulo M S Lima
AU - José Carlos M Mombach
AU - Shantanu Gupta
PY - 2026
DA - 2026/09/22
JO - International journal of molecular sciences
DO - 10.3390/ijms27198441
UR - https://europepmc.org/article/MED/42883693
AB - 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-1β 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-SNHG7-miR-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-SNHG7-miR-34a axis in HCC.
SN - 1422-0067
ER -