{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T02:04:14Z","timestamp":1779674654488,"version":"3.53.1"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology, Ministry of Science and Technology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality, with poor survival outcomes despite advances in surgery, chemotherapy, targeted therapy, and immunotherapy. The tumor microenvironment (TME) plays a central role in sustaining tumor growth, immune evasion, and systemic metabolic dysfunction. In this study, we performed an integrative analysis of differentially expressed microRNAs (miRNAs) to uncover their contributions to dysregulated signaling networks in NSCLC. hsa-miR-486-5p was identified as a prominent differentially expressed candidate miRNA. Using mathematical modeling and regression-based reduction, we identified Forkhead Box O1 (FOXO1) and Unc-51 like Autophagy Activating Kinase 2 (ULK2) as critical regulatory nodes that integrate oncogenic signaling with cellular homeostasis. Aberrant expression of hsa-miR-486-5p was found to modulate pathways including PI3K\/AKT\/mTOR, NF-\u03baB, and JAK-STAT3, thereby promoting tumor progression and secretion of inflammatory cytokines. These cytokines, viz., IL-6, TNF-\u03b1, and IL-1\u03b2, activate muscle-specific protein degradation pathways through E3 ubiquitin ligases TRIM63 and FBXO32, linking NSCLC progression to cancer-associated sarcopenia. Quasipotential landscape analysis further revealed dynamic phenotypic transitions between stable and unstable states, highlighting the adaptability of tumor\u2013host interactions. Collectively, our findings demonstrate that miRNA-mediated regulatory networks not only drive NSCLC progression and inflammation but also contribute to systemic muscle wasting. These insights emphasize the need for novel therapeutic strategies, including RNA-based interventions, to overcome resistance, improve survival, and address the metabolic complications associated with NSCLC.<\/jats:p>","DOI":"10.3390\/ijms27114703","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:45:08Z","timestamp":1779673508000},"page":"4703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["miRNA-Mediated Signaling Networks in Non-Small Cell Lung Cancer: Linking Tumor Progression to Sarcopenia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4594-2218","authenticated-orcid":false,"given":"Swati","family":"Goswami","sequence":"first","affiliation":[{"name":"Systems Medicine Laboratory, BRIC\u2014National Centre for Cell Science, National Centre for Cell Science Complex, SPPU Campus, Ganeshkhind, Pune 411007, India"},{"name":"Regional Centre for Biotechnology, Faridabad 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-4724","authenticated-orcid":false,"given":"Pooja","family":"Gulhane","sequence":"additional","affiliation":[{"name":"Systems Medicine Laboratory, BRIC\u2014National Centre for Cell Science, National Centre for Cell Science Complex, SPPU Campus, Ganeshkhind, Pune 411007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailza","family":"Singh","sequence":"additional","affiliation":[{"name":"Systems Medicine Laboratory, BRIC\u2014National Centre for Cell Science, National Centre for Cell Science Complex, SPPU Campus, Ganeshkhind, Pune 411007, India"},{"name":"Regional Centre for Biotechnology, Faridabad 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3390\/epidemiologia5040053","article-title":"Global, regional, and national burden of tracheal, bronchus, and lung cancer in 2022: Evidence from the GLOBOCAN study","volume":"5","author":"Sharma","year":"2024","journal-title":"Epidemiologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.4103\/ijmr.ijmr_1364_21","article-title":"Clinicoepidemiological profile of lung cancers in India: Results from the National Cancer Registry Programme","volume":"155","author":"Nath","year":"2022","journal-title":"Indian J. 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