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The study identified long non-coding RNA (lncRNA)-encoded peptides in esophageal squamous cell carcinoma (ESCC) using a combination of methods, including gene co-expression network analysis, ribosome footprints, ORF prediction, mass spectrometry, and western blotting. Six lncRNA open reading frames with peptide-coding abilities were identified, including KDM4A-AS1 ORF. The KDM4A-AS1-encoded peptide inhibited ESCC cell viability and migratory ability by interacting with proteins related to fatty acid metabolism and redox process. The peptide also reduced stearoyl-CoA desaturase and fatty acid synthase expression, increased reactive oxygen species level, and reduced mitochondrial membrane potential in ESCC cells. This study provides novel strategies for identifying lncRNA-encoded peptides and insights into their potential roles in ESCC.
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