Mitochondrial Bioenergetic Remodeling Associated with LCRMP-1 Expression in Lung Adenocarcinoma
DOI:
https://doi.org/10.64229/47kkw106Keywords:
Lung adenocarcinoma, LCRMP-1, Mitochondrial dysfunction, Transcriptomic analysis, Protein-protein interaction network, Prognostic biomarkersAbstract
Lung adenocarcinoma, the most common subtype of non-small cell lung cancer (NSCLC), is marked by metabolic reprogramming and mitochondrial dysregulation. Long-form collapsin response mediator protein-1 (LCRMP-1) is implicated in tumor progression, but its role in mitochondrial transcriptional regulation remains unclear. Using publicly available microarray data (GSE308874) from lung adenocarcinoma cell lines with LCRMP-1 overexpression or silencing, differentially expressed genes (DEGs) were identified, and mitochondrial-associated genes were analyzed via Gene Ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) enrichment, protein-protein interaction (PPI), co-expression, and network clustering. Transcriptomic factor enrichment and drug perturbation analyses were performed to uncover upstream regulators and therapeutic targets, and prognostic relevance was assessed using Kaplan-Meier survival analysis. LCRMP-1 modulation induced widespread transcriptomic changes, prominently affecting mitochondrial genes involved in oxidative phosphorylation (OXPHOS), respiration, redox balance, and metabolism. Network analysis revealed a core mitochondrial module including CYCS, NDUFAB1, TUFM, VDAC1, TOMM20, ETFA, SSBP1, and SUCLA2, regulated by PRDM2, MLX, E2F4, and HMGN3, with drug perturbation profiles indicating potential pharmacological interventions. Several mitochondrial genes, notably TUFM and CYCS, correlated significantly with patient survival. This integrative study highlights LCRMP-1-mediated mitochondrial reprogramming as a key feature of lung adenocarcinoma and identifies hub genes and regulators as potential biomarkers and therapeutic targets.
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