Long noncoding RNAs with peptide-encoding potential identified in esophageal squamous cell carcinoma:...

Area of Science:

• Molecular Biology
• Genomics
• Cancer Research

Background:

• Knowledge regarding long noncoding RNA (lncRNA)-encoded peptides in esophageal squamous cell carcinoma (ESCC) is limited.
• Identifying functional lncRNA-derived peptides is crucial for understanding cancer biology.

Purpose of the Study:

• To identify novel peptide-coding long noncoding RNAs (lncRNAs) in esophageal squamous cell carcinoma (ESCC).
• To investigate the functional role of the KDM4A-AS1 ORF-encoded peptide in ESCC progression.

Main Methods:

• Weighted gene co-expression network analysis (WGCNA) of ESCC clinical samples.
• Ribosome footprinting, open reading frame (ORF) prediction, mass spectrometry (MS), and western blotting.
• Co-immunoprecipitation and cellular/molecular experiments to determine protein interactions and functional impact.

Main Results:

• Six lncRNA ORFs with peptide-coding potential were identified, including KDM4A-AS1.
• The KDM4A-AS1-encoded peptide significantly reduced ESCC cell viability and migration.
• The peptide interacted with 103 proteins involved in fatty acid metabolism and redox processes, inhibiting key enzymes and altering cellular energetics.

Conclusions:

• Multiple lncRNAs with translational potential were simultaneously identified in ESCC using a multi-omics approach.
• The lncRNA KDM4A-AS1-encoded peptide acts as a tumor suppressor by modulating fatty acid metabolism and redox balance in ESCC.
• This study provides novel strategies for identifying lncRNA-encoded peptides and highlights their potential as therapeutic targets.