{"doi":"10.3390/biom15111564","title":"LncRNA-Mediated miR-145 Sponging Drives FN1 and CCND1 Expression: Prognostic and Therapeutic Targets in NSCLC","abstract":"<b>Background:</b> 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. <b>Methods:</b> Integrated transcriptomic analysis of NSCLC datasets (GSE135304: blood RNA from 712 patients; GSE203510: plasma miRNAs) was used to identify dysregulated genes (|log2FC| > 0.1, <i>p</i> < 0.05) and miRNAs (|log2FC| > 1, <i>p</i> < 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. <b>Results:</b> We identified 8271 dysregulated genes and 52 miRNAs. miR-145-3p, critical in immune regulation, was significantly downregulated (log2FC = -1.24, <i>p</i> = 0.036). Intersection analysis revealed 27 miR-145-3p targets (e.g., FN1, CCND1, SMAD3) enriched in immune pathways (FDR < 0.05) and TGF-β-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 (<i>p</i> < 0.05). GEPIA revealed a significant FN1-CCND1 co-expression (<i>p</i> = 0.0017). <b>Conclusions:</b> We characterize a novel LOC729919/LOC100134412-miR-145-FN1/CCND1 ceRNA axis in NSCLC pathogenesis. FN1's prognostic value and functional linkage to CCND1 underscores its potential clinical relevance for therapeutic disruption.","journal":"Biomolecules","year":2025,"id":11575,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-11-06","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":92356,"name":"Davar Amani","orcid":"0000-0001-7277-4484","position":1,"is_corresponding":false},{"id":92357,"name":"Babak Salimi","orcid":"0000-0002-5541-8434","position":2,"is_corresponding":false},{"id":20867,"name":"Ian M. Adcock","orcid":"0000-0003-2101-8843","position":3,"is_corresponding":false},{"id":92358,"name":"Esmaeil Mortaz","orcid":"0000-0002-7753-9624","position":4,"is_corresponding":false},{"id":92355,"name":"Safa Tahmasebi","orcid":"0000-0002-8598-1922","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}