LncRNA-mediated miR-145 sponging drives FN1 and CCND1 expression: prognostic and therapeutic targets in NSCLC
File(s)
Published version
Author(s)
Tahmasebi, Safa
Amani, Davar
Salimi, Babak
Adcock, Ian
Mortaz, Esmaeil
Type
Journal Article
Abstract
Background: Non-small cell lung cancer (NSCLC) progression is driven by dysregulated competing endogenous RNA (ceRNA) networks, where non-coding RNAs sequester miR-NAs 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| > 0.1, p < 0.05) and miRNAs (|log2FC| > 1, p < 0.05). Experimentally validated targets from miRTarBase/TarBase were intersected with dysreg-ulated genes, followed by WikiPathways/GO enrichment. ceRNA networks were con-structed 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 = −1.24, p = 0.036). Intersec-tion analysis revealed 27 miR-145-3p targets (e.g., FN1, CCND1, SMAD3) enriched in im-mune 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, dere-pressing the expression of the metastasis drivers FN1 (ECM regulator) and CCND1 (cell cycle controller). This ceRNA axis operates within a broader dysregulation of ATM-de-pendent DNA damage, Hippo signaling, and cell cycle pathways. RT-qPCR confirmed significant miR-145-3p suppression in NSCLC models (p < 0.05). GEPIA revealed a signif-icant FN1-CCND1 co-expression (p = 0.0017). Conclusion: 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.
Date Issued
2025-11-01
Date Acceptance
2025-10-20
Citation
Biomolecules, 2025, 15 (11)
ISSN
2218-273X
Publisher
MDPI AG
Journal / Book Title
Biomolecules
Volume
15
Issue
11
Copyright Statement
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).
License URL
Publication Status
Published
Article Number
1564
Date Publish Online
2025-11-06