{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:39Z","timestamp":1792789119951,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU-IMI2","award":["EU-IMI2 831434"],"award-info":[{"award-number":["EU-IMI2 831434"]}]},{"name":"MRC","award":["MR\/T010371\/1"],"award-info":[{"award-number":["MR\/T010371\/1"]}]},{"name":"MUCOSA","award":["MR\/Z506576\/1"],"award-info":[{"award-number":["MR\/Z506576\/1"]}]},{"name":"ARC","award":["DP230101156"],"award-info":[{"award-number":["DP230101156"]}]},{"name":"NIH","award":["5R01ES035457-03"],"award-info":[{"award-number":["5R01ES035457-03"]}]},{"name":"RESPIRE-EXCEL","award":["APP48641"],"award-info":[{"award-number":["APP48641"]}]},{"DOI":"10.13039\/501100000266","name":"EPSRC","doi-asserted-by":"crossref","award":["EP\/Y018680\/1"],"award-info":[{"award-number":["EP\/Y018680\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Non-small cell lung cancer (NSCLC) progression is driven by dysregulated competing endogenous RNA (ceRNA) networks, where non-coding RNAs sequester miRNAs to modulate oncogene expression. The tumor-suppressor miR-145 is frequently downregulated in NSCLC, but its lncRNA-mediated regulation remains incompletely characterized. Methods: Integrated transcriptomic analysis of NSCLC datasets (GSE135304: blood RNA from 712 patients; GSE203510: plasma miRNAs) was used to identify dysregulated genes (|log2FC| &gt; 0.1, p &lt; 0.05) and miRNAs (|log2FC| &gt; 1, p &lt; 0.05). Experimentally validated targets from miRTarBase\/TarBase were intersected with dysregulated genes, followed by WikiPathways\/GO enrichment. ceRNA networks were constructed via co-expression analysis. RT-qPCR validated miR-145-3p expression in A549\/MRC-5 cells and NSCLC tissues. GEPIA assessed FN1\/CCND1 clinical relevance. Results: We identified 8271 dysregulated genes and 52 miRNAs. miR-145-3p, critical in immune regulation, was significantly downregulated (log2FC = \u22121.24, p = 0.036). Intersection analysis revealed 27 miR-145-3p targets (e.g., FN1, CCND1, SMAD3) enriched in immune pathways (FDR &lt; 0.05) and TGF-\u03b2-mediated EMT within the dysregulated geneset. Six immune-linked hub genes emerged. LncRNAs LOC729919 and LOC100134412 showed strong co-expression with hub genes and competitively bind miR-145-3p, derepressing the expression of the metastasis drivers FN1 (ECM regulator) and CCND1 (cell cycle controller). This ceRNA axis operates within a broader dysregulation of ATM-dependent DNA damage, Hippo signaling, and cell cycle pathways. RT-qPCR confirmed significant miR-145-3p suppression in NSCLC models (p &lt; 0.05). GEPIA revealed a significant FN1-CCND1 co-expression (p = 0.0017). Conclusions: We characterize a novel LOC729919\/LOC100134412\u2013miR-145\u2013FN1\/CCND1 ceRNA axis in NSCLC pathogenesis. FN1\u2019s prognostic value and functional linkage to CCND1 underscores its potential clinical relevance for therapeutic disruption.<\/jats:p>","DOI":"10.3390\/biom15111564","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"1564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["LncRNA-Mediated miR-145 Sponging Drives FN1 and CCND1 Expression: Prognostic and Therapeutic Targets in NSCLC"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8598-1922","authenticated-orcid":false,"given":"Safa","family":"Tahmasebi","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davar","family":"Amani","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Salimi","sequence":"additional","affiliation":[{"name":"Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Adcock","sequence":"additional","affiliation":[{"name":"Respiratory Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-9624","authenticated-orcid":false,"given":"Esmaeil","family":"Mortaz","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran"},{"name":"Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran"},{"name":"Respiratory Immunology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41572-024-00551-9","article-title":"Non-small-cell lung cancer","volume":"10","author":"Hendriks","year":"2024","journal-title":"Nat. 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