Currently, the knowledge of long noncoding RNA (lncRNA)-encoded peptides is quite lacking in esophageal squamous cell carcinoma (ESCC). In this study, we simultaneously identified six lncRNA open reading frames (ORFs) with peptide-coding abilities including lysine-specific demethylase 4A antisense RNA 1 (KDM4A-AS1) ORF by combining weighted gene co-expression network analysis (WGCNA) for ESCC clinical samples, ribosome footprints, ORF prediction, mass spectrometry (MS) identification, and western blotting. KDM4A-AS1 ORF-encoded peptide reduced ESCC cell viability and migratory ability. Co-immunoprecipitation and MS analysis revealed that KDM4A-AS1-encoded peptide specifically bound with 103 proteins in ESCC cells, and enrichment analysis suggested that peptide-bound proteins were related to fatty acid metabolism and redox process. Cell and molecular experiments demonstrated that KDM4A-AS1-encoded peptide inhibited stearoyl-CoA desaturase and fatty acid synthase expression, increased reactive oxygen species level, and reduced mitochondrial membrane potential in ESCC cells. In summary, multiple lncRNAs with translation potential were simultaneously identified by combining multiple approaches in ESCC, providing novel identification strategies for lncRNA-encoded peptides. Moreover, lncRNA KDM4A-AS1-encoded peptide weakened ESCC cell viability and migratory capacity and functioned in fatty acid metabolism and redox process.
Keywords: KDM4A-AS1; esophageal squamous cell carcinoma; lncRNAs; mass spectrometry; peptide.
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.