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miRNA-Mediated Signaling Networks in Non-Small Cell Lung Cancer: Linking Tumor Progression to Sarcopenia
Swati Goswami1,2, Pooja Gulhane1, Shailza Singh1,2
1Systems Medicine Laboratory, BRIC-National Centre for Cell Science, National Centre for Cell Science Complex, SPPU Campus, Ganeshkhind, Pune 411007, India.
International Journal of Molecular Sciences
|June 12, 2026
Summary
This study reveals how microRNAs (miRNAs) drive non-small cell lung cancer (NSCLC) progression and inflammation, leading to muscle wasting. Novel RNA-based therapies could improve survival and metabolic health in NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Systems Biology
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality, with the tumor microenvironment (TME) crucial for tumor progression and immune evasion.
- Despite advances, NSCLC outcomes remain poor, necessitating deeper understanding of underlying molecular mechanisms.
- The TME influences systemic metabolism and immune responses, contributing to cancer-associated morbidity.
Purpose of the Study:
- To investigate the role of differentially expressed microRNAs (miRNAs) in NSCLC signaling networks using integrative analysis.
- To identify key regulatory nodes and pathways influenced by miRNAs in NSCLC pathogenesis.
- To explore the link between NSCLC progression, inflammation, and systemic metabolic dysfunction, specifically cancer-associated sarcopenia.
Main Methods:
- Integrative analysis of differentially expressed miRNAs in NSCLC.
- Mathematical modeling and regression-based reduction to identify regulatory nodes (FOXO1, ULK2).
- Analysis of modulated signaling pathways (PI3K/AKT/mTOR, NF-κB, JAK-STAT3) and cytokine secretion (IL-6, TNF-α, IL-1β).
- Investigation of E3 ubiquitin ligases (TRIM63, FBXO32) in muscle protein degradation.
- Quasipotential landscape analysis for dynamic phenotypic transitions.
Main Results:
- hsa-miR-486-5p identified as a key differentially expressed miRNA.
- FOXO1 and ULK2 identified as critical regulatory nodes integrating oncogenic signaling and homeostasis.
- Aberrant hsa-miR-486-5p expression modulates PI3K/AKT/mTOR, NF-κB, and JAK-STAT3 pathways, promoting tumor progression and inflammation.
- NSCLC-induced cytokines activate muscle-specific protein degradation via TRIM63 and FBXO32, linking cancer to sarcopenia.
- Dynamic phenotypic transitions observed, highlighting tumor-host interaction adaptability.
Conclusions:
- miRNA-mediated networks drive NSCLC progression, inflammation, and systemic muscle wasting (cancer-associated sarcopenia).
- Dysregulated miRNAs contribute to metabolic complications and poor survival in NSCLC.
- Novel therapeutic strategies, including RNA-based interventions, are needed to overcome resistance and improve patient outcomes.
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