OIP5 drives malignant progression of lung adenocarcinoma as revealed by multi-omics and functional validation

Lung adenocarcinoma (LUAD) generally presents an unfavorable clinical prognosis. Opa-interacting protein 5 (OIP5) is aberrantly expressed in various malignancies, but its molecular role in LUAD is not well understood. Herein, this study comprehensively investigated the biomarker potential of OIP5 in LUAD by elucidating its clinical relevance, expression profiling characteristics, upstream regulatory circuitry, and oncogenic biological behaviors. An in-house immunohistochemistry (IHC) assay was conducted on 75 LUAD specimens and 75 non-tumor lung tissues to detect OIP5 protein expression levels. Multi-center GEO and TCGA datasets were integrated for meta-analysis to assess OIP5 mRNA expression in LUAD tissues. Differential expression and Weighted Gene Co-expression Network Analysis (WGCNA) were used to screen key genes co-expressed with OIP5, followed by enrichment analysis. Immune infiltration and single-cell analyses revealed OIP5’s relationship with the tumor microenvironment. Lentivirus-mediated OIP5 knockdown was implemented in A549 and 95D cells, and the impacts of OIP5 depletion on cell proliferation and migration were evaluated using CCK-8, colony formation, flow cytometry, wound-healing, and transwell migration assays. OIP5 expression was notably increased in LUAD tissues, and its elevated levels were strongly linked to unfavorable clinicopathological features. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that OIP5-related genes were enriched in cell cycle-related pathways, such as cell division and chromosome segregation. Several transcription factors, including E2F1, E2F6, and NFIC, were identified as predicted candidate regulators of OIP5 expression. Immune infiltration profiling demonstrated an inverse correlation between OIP5 expression and both immune and stromal scores. Single-cell transcriptomic analysis further verified that OIP5 was specifically overexpressed in proliferative cell subsets and OIP5 expression was associated with stemness-related features. Drug sensitivity analysis suggested that increased OIP5 expression was associated with enhanced responsiveness to multiple anti-tumor agents. Moreover, the reduction of OIP5 expression markedly repressed the proliferation and migration capabilities of A549 and 95D lung adenocarcinoma cells in vitro. OIP5 is significantly upregulated in LUAD, and is closely correlated with unfavorable clinicopathological characteristics. It acts as an oncogene by driving cell cycle progression and promoting the proliferation and migration of LUAD cells, and is associated with alterations in the tumor immune microenvironment.