C1ORF112 drives lung adenocarcinoma progression through e2f8-mediated transcriptional activation.

BACKGROUNDLung adenocarcinoma (LUAD) remains a leading cause of cancer mortality, with poor prognosis driven by metastasis and therapeutic resistance. Chromosome 1 open reading frame 112 (C1ORF112) encodes a nuclear protein involved in DNA replication and repair, but its role in LUAD is unclear. To systematically investigate the clinical relevance, functional impact, and transcriptional regulation of C1ORF112 in LUAD through integrative bioinformatic and experimental approaches.

METHODSC1ORF112 expression and prognostic significance were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Single-cell RNA sequencing defined cellular localization and communication patterns. Functional enrichment, protein-protein interaction (PPI), and transcription factor prediction analyses were performed. In vitro assays and xenograft models assessed biological functions and transcriptional regulation by E2F8.

RESULTSC1ORF112 was significantly upregulated in LUAD and correlated with poor overall survival (OS). Single-cell analysis showed elevated expression in malignant cells, fibroblasts, endothelial cells, and mast cells, accompanied by increased communication with M2 macrophages and exhausted CD8+ T cells. Overexpression of C1ORF112 inhibited apoptosis and promoted proliferation in LUAD cells, while xenografts exhibited accelerated tumor growth and increased Ki67 expression. Mechanistically, E2F8 directly bound the C1ORF112 promoter, enhancing its transcription and inhibiting downstream p53 signaling.

CONCLUSIONSOur integrative analysis suggests that C1ORF112 exhibits oncogenic properties in LUAD by promoting tumor survival, proliferation, and potentially remodeling the tumor microenvironment. The transcriptional activation by E2F8 highlights the E2F8-C1ORF112 axis as a candidate prognostic biomarker and therapeutic vulnerability, though prospective clinical validation and drug sensitivity studies are warranted.