LncRNA-encoded micropeptides: Emerging regulators of cancer metabolism and precision oncology

Long noncoding RNAs (lncRNAs) have traditionally been classified as non-protein-coding transcripts, yet recent advances in ribosome profiling and proteogenomics have revealed that some lncRNAs encode functional micropeptides. These micropeptides, typically fewer than 100 amino acids, play pivotal roles in cancer progression by modulating signaling pathways, metabolic reprogramming, and therapeutic implication. Despite challenges in detection due to their low abundance, emerging technologies like mass spectrometry and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based validation are accelerating their discovery. This review synthesizes current knowledge on lncRNA-derived micropeptides in cancer, emphasizing their mechanisms, clinical implications, and therapeutic promise. By bridging the gap between noncoding RNA biology and proteomics, these micropeptides represent a transformative frontier in cancer research and treatment.